title: Managing the effect of TRIPS on availability of priority vaccines.

text: The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.


title: Wearing masks in a pediatric hospital: developing practical guidelines.

text: During the outbreak of Severe Acute Respiratory Syndrome (SARS) in the spring of 2003, strict infection control measures were implemented in Toronto and surrounding hospitals. These measures included extreme restrictions on those who would normally accompany patients to the hospital, screening for SARS, and protective attire for hospital staff, including masks, face shields, goggles, gloves and gowns. At Toronto's Hospital for Sick Children (HSC), patients could only be accompanied or visited by one person, often only in patients' rooms. For the first four weeks, patients and their designated parent had to wear masks in almost all areas of the hospital. Staff wore masks (and other appropriate protective clothing) whenever in contact with patients and in many patient care areas. Although these barriers were an important part of containing SARS, their use created significant challenges for patients and staff. This article focusses on the use of infection control masks in routine pediatric healthcare and the tools developed by HSC staff to reduce the negative psychosocial impact on children and families.


title: Progressive dyspnea associated with a crazy-paving appearance on a chest computed tomography scan.

text: A 'crazy-paving' appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information.


title: Cirrhosis associated with the Australia antigen in an infant who acquired hepatitis from her mother.

text: A 19-week-old English girl developed acute viral hepatitis, which became chronic with persistent hepatosplenomegaly and abnormal liver function tests. Liver biopsy at 1 year showed an active cirrhosis with multinucleated giant cells. The Australia (Au) antigen was detected repeatedly in the infant's serum by immunodiffusion and by electron microscopy at the time of the acute attack and during the development of cirrhosis. She had apparently acquired the hepatitis from her mother, who had had jaundice at the end of pregnancy and for one month thereafter, and who was subsequently shown to be a carrier of Au antigen. Particles with surface projections resembling paramyxoviruses were observed in two of the later specimens of the infant's serum.


title: Attitude, beliefs, and intentions to care for SARS patients among Korean clinical nurses: an application of theory of planned behavior.

text: PURPOSE This study examined Korean clinical nurses' intentions to care for SARS patients and identify determinants of the intentions. Theory of planned behavior was the framework to explain the intentions of Korean nurses for SARS patients care. METHODS A convenient sample of six hundreds and seventy nine clinical nurses from four university-affiliated hospitals located in Seoul and in Kyung-gi province was used. Self-administered (83-items) questionnaire was used to collect data. Intentions, attitude, subjective norm, perceive behavioral control, behavioral beliefs, normative beliefs, and control beliefs were the study variables. All items were measured using 7-point Likert scale (-3 to +3). Data were analyzed using descriptive statistics, Pearson correlation method, and stepwise multiple regression methods. RESULTS Intentions and attitudes toward SARS patient care among Korean clinical nurses were moderate, but their subjective norm and perceive behavioral control of SARS patients care were negative. Stepwise multiple regression analysis indicated that attitude toward SARS patient care, perceived behavioral control, subjective norm were the determinants of the intentions for SARS patients care as theory proposed. Among the behavioral beliefs, "SARS-patient caring would be a new experience", "during SARS-patient caring, I should be apart from my family", "after completing SARS-patient caring, I would be proud of myself being able to cope with a stressful event" and "with my SARS-patient caring, patients could recover from SARS" were the significant determinants. Among the normative beliefs, colleague approval, spouse approval, and physician approval were significant determinants of the intentions. Among the control beliefs, "SARS-patient caring would be a challenge" "SARS-patient caring is a professional responsibility", "tension during the care of SARS patients" and "support from team members" were the significant determinants of the intentions. CONCLUSIONS Korean clinical nurses in this study were not willing to care for SARS patients and showed negative attitude toward the care. They believed their friends and family were not approved their care for SARS patients. Nurses were in conflicts between professional responsibilities to care for SARS patients and personal safety. This study was the first to understand stress and burden of Korean clinical nurses who are in front line to care for newly developed communicable disease such as SARS. Under the circumstance where several fatal communicable diseases are predictable, conflicts between professional responsibility and their personal risks should be taken into considerations by nurses themselves and by nursing administrators in order to improve quality of care.


title: Infectious agents associated with respiratory disease in pheasants.

text: In a case-control study of the infectious agents associated with natural outbreaks of respiratory disease in pheasants, 28 batches of birds from sites affected by disease and eight batches of birds from unaffected sites were examined by six veterinary laboratories in England, Wales and Scotland, and tested for mycoplasmas, other bacteria and viruses. Sinusitis was the commonest sign of disease and was associated with Mycoplasma gallisepticum as detected by PCR in the trachea (P < 0.05) and conjunctiva (P < 0.01). Sinusitis was also associated with pasteurella cultured from the sinus (P < 0.05), antibody to avian pneumovirus (APV) (P < 0.01) and avian coronaviruses as detected by reverse-transcriptase PCR (P < 0.05); there was no association between disease and APV as detected by PCR. Avian coronaviruses were the most common infectious agents detected. They were genetically close to infectious bronchitis virus (IBV) but differed in their gene sequence from all the serotypes of IBV previously identified in domestic fowl, and serological tests with six known IBV types showed little cross reactivity. Mycoplasma species other than M gallisepticum were cultured in 18 batches of pheasants but, with the exception of Mycoplasma gallinaceum, were not associated with disease.


title: [The first case of severe acute respiratory syndrome in Foshan].

text: OBJECTIVE To evaluate the epidemiologic feature, diagnosis and treatment of severe acute respiratory syndrome (SARS). METHODS To describe the epidemiologic and clinical features of the first case of SARS in Foshan city, Guangdong province retrospectively, and to review the diagnostic procedure. RESULTS This case had the following features: (1) a history of contact with mild cats and eating the animal's meat; (2) high fever (temperature, > 38 degrees C), followed by dry cough, rapid progression to respiratory failure, followed by radiographic evidence of bilateral air-space lesions; (3) no leukocytosis; (4) spread to 4 family members who had had direct contact with this patient; (5) the patient's serum SARS virus IgG was confirmed to be positive; (6) the patient was treated with anti-viral agents, antibiotics and mechanical ventilation and molecular adsorbent re-circulating system (MARS). CONCLUSIONS The clinical manifestations of the SARS case, which was highly infectious, met world health organization (WHO) criteria for the diagnosis of SARS. Early initiation of mechanical ventilation and supportive therapy contributed to the good prognosis of this critical case.


title: Norovirus and histo-blood group antigens.

text: Norovirus (NoV), a member of the family Caliciviridae, is a major cause of acute water- and food-borne nonbacterial gastroenteritis and forms antigenically diverse groups of viruses. Human NoVs are divided into at least three genogroups, genogroups I (GI), GII, and GIV, which contain at least 15, 18, and 1 genotypes, respectively. Except for a few genotypes, all NoVs bind to histo-blood group antigens (HBGAs), namely ABH antigens and Lewis antigens, in which carbohydrate core structures, (types 1 and 2) constitute antigenically distinct phenotypes. Volunteer challenge studies have indicated that carbohydrate binding is essential for genogroup I genotype 1 (GI/1) infection. Non-secretors who do not express FUT2 fucosyltransferase, and consequently do not express H type 1 or Lewis b antigens in the gut, are not infected after challenge with GI/1. NoV virus-like particles (VLPs), which are recombinant particles that are morphologically and antigenically similar to the native virion, display different ABH and Le carbohydrate-binding profiles in vitro. Epidemiological studies have shown that individuals with different ABH phenotypes are infected with NoV strains in a genotype-specific manner. On the other hand, an in vitro binding assay using NoV VLPs showed a uniform recognition pattern against type 1 and 2 core structures, and bind more tightly to type 1 carbohydrates than to type 2. Type 1 carbohydrates are expressed at the surface of the small intestine and are presumably targeted by NoV. This property may afford NoV tissue specificity. GII/4 includes global epidemic strains and binds to more HBGAs than other genogroups. This characteristic may be linked to the worldwide transmission of GII/4 strains. Although it is still unclear whether HBGAs act as primary receptors or enhance NoV infectivity, they are important factors in determining tissue specificity and the risk of transmission.


title: Use of tissue glues in endoscopic pituitary surgery: a cost comparison.

text: BACKGROUND Post-operative cerebrospinal fluid (CSF) leaks are a common complication of endoscopic pituitary surgery and account for a significant proportion of hospital costs associated with this procedure. Tisseel® is a tissue glue commonly used as an adjunct in dural repair but is not optimal for this purpose. DuraSeal® has several properties advantageous for dural repair but is not widely accepted in Canada partly due to its increased cost. OBJECTIVE A cost analysis of DuraSeal® versus Tisseel® in endoscopic pituitary surgery. METHODS A cost analysis was performed based on typical endoscopic pituitary surgery cases performed at our tertiary care institution. Operating room, hospital admission, and surgical sealant costs were obtained directly while estimates of patient recovery time and post-operative CSF leak rates were based on consensus values reported in the literature. Outcomes were reported for various possible clinical scenarios of sealant use. RESULTS In a model where surgical sealant is employed only in high-risk cases, use of DuraSeal® allows for a yearly cost savings of at least $4486.72. If surgical sealant is used in all cases, regular use of DuraSeal® versus Tisseel® either marginally reduces yearly costs or increases them by a maximum of $7619.25, depending on the case volume and estimated post-operative CSF leak rate. CONCLUSION In most clinical scenarios, use of DuraSeal® in endoscopic pituitary surgery may reduce overall yearly hospital costs compared to Tisseel®.


title: [Immunofluorescent diagnosis of rota-, corona- and pestivirus infections in calves].

text: Bovine hyperimmune fluorescent sera were obtained for indication of the rota- and corona-virus infections in calves, which were highly specific and of immunofluorescent titers within the 1:32-64 range. Their testing was carried out via the direct immunofluorescence method, using histologic cross-sectioned material and impression preparations of the mucous membrane of calves died of enteritis as well as cell cultures of fetal calf kidney and organic cultures of calf trachea all contaminated, resp., infected with feces. The study of the intestinal membrane of a total of 100 diseased calves, employing this method, has demonstrated a rotavirus antigen in 38.0 per cent of the cases, and a coronavirus one--in 37.0 per cent. The causative agent of mucous disease (a pestivirus) was demonstrated by means of the respective conjugate in 47.3 per cent of the cases, using abomasal membrane of a total of 55 calves. Rota- and corona-virus infections were also established in the abomasal membrane of diseased calves, and pesti-virus infections--in the intestinal mucosa as well. Established were also mixed infections with the three viruses taking part at various combinations. A celloidin method was worked out for making immunofluorescent preparations of infected monolayer cell cultures. In the cell cultures infected with feces the totavirus antigen was demonstrated in 19.4 per cent of the cases, and the coronavirus one--in 25.6 per cent.


title: [Medication and comedication in COVID-19 patients].

text: This paper discusses the possible effects of comedication on COVID-19 and the current treatment options for this infection. It is very doubtful that comedication has a disadvantageous effect on the course of the disease. NSAIDs should be avoided in any patient with a possible severe disease, because of potential side effects. Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems. There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors. Currently, chloroquine and remdesivir are possible treatment options. There is no sound evidence for either treatment. Chloroquine has side effects (nausea, QT prolongation) and there are several drug interactions. The treatment should be reconsidered in the event of side effects and when inferior medication for comorbidity must be prescribed because of possible interactions. Lopinavir/ritonavir is not effective. Supportive care is at present the mainstay of the treatment.


Technical considerations for developing enzyme immunohistochemical staining procedures on formalin-fixed paraffin-embedded tissues for diagnostic pathology.


title: The missing link between human ecology and public health: the case of cancer.

text: OBJECTIVES The primary role played by the 'ecological context' in clarifying the causes and dynamics of human health and disease is the topic of this article. It emphasizes that the challenging incidence of cancer and other diseases can be charged primarily to the effects of the worldwide dominant economic model. METHODS Human culture may act as a powerful force affecting the environment, biology and health of humans and other species. Human culture can be viewed as a special and extreme case of 'niche construction', where human-specific traits, technologies and beliefs act together. RESULTS The feedback between human activities and the environment can promote different trends in public health. This should provide the opportunity to rethink the consequences that our economic model produces both on the environment and on physical, mental and social health of our species.


title: Multigene RNA vector based on coronavirus transcription.

text: Coronavirus genomes are the largest known autonomously replicating RNAs with a size of ca. 30 kb. They are of positive polarity and are translated to produce the viral proteins needed for the assembly of an active replicase-transcriptase complex. In addition to replicating the genomic RNA, a key feature of this complex is a unique transcription process that results in the synthesis of a nested set of six to eight subgenomic mRNAs. These subgenomic mRNAs are produced in constant but nonequimolar amounts and, in general, each is translated to produce a single protein. To take advantage of these features, we have developed a multigene expression vector based on human coronavirus 229E. We have constructed a prototype RNA vector containing the 5' and 3' ends of the human coronavirus genome, the entire human coronavirus replicase gene, and three reporter genes (i.e., the chloramphenicol acetyltransferase [CAT] gene, the firefly luciferase [LUC] gene, and the green fluorescent protein [GFP] gene). Each reporter gene is located downstream of a human coronavirus transcription-associated sequence, which is required for the synthesis of individual subgenomic mRNAs. The transfection of vector RNA and human coronavirus nucleocapsid protein mRNA into BHK-21 cells resulted in the expression of the CAT, LUC, and GFP reporter proteins. Sequence analysis confirmed the synthesis of coronavirus-specific mRNAs encoding CAT, LUC, and GFP. In addition, we have shown that human coronavirus-based vector RNA can be packaged into virus-like particles that, in turn, can be used to transduce immature and mature human dendritic cells. In summary, we describe a new class of eukaryotic, multigene expression vectors that are based on the human coronavirus 229E and have the ability to transduce human dendritic cells.


title: A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory syndrome (SARS) coronavirus spike protein transmembrane domain.

text: In an attempt to understand what distinguishes severe acute respiratory syndrome (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched for elements that are unique to its proteins and not present in any other family member. We identified an insertion of two glycine residues, forming the GxxxG motif, in the SCoV spike protein transmembrane domain (TMD), which is not found in any other coronavirus. This surprising finding raises an "oligomerization riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike protein is known to be trimeric. Using an in vivo assay, we found that the SCoV spike protein TMD is oligomeric and that this oligomerization is driven by the GxxxG motif. We also found that the GxxxG motif contributes toward the trimerization of the entire spike protein; in that, mutations in the GxxxG motif decrease trimerization of the full-length protein expressed in mammalian cells. Using molecular modeling, we show that the SCoV spike protein TMD adopts a distinct and unique structure as opposed to all other coronaviruses. In this unique structure, the glycine residues of the GxxxG motif are facing each other, enhancing helix-helix interactions by allowing for the close positioning of the helices. This unique orientation of the glycine residues also stabilizes the trimeric bundle during multi-nanosecond molecular dynamics simulation in a hydrated lipid bilayer. To the best of our knowledge, this is the first demonstration that the GxxxG motif can potentiate other oligomeric forms beside a dimer. Finally, according to recent studies, the stabilization of the trimeric bundle is linked to a higher fusion activity of the spike protein, and the possible influence of the GxxxG motif on this feature is discussed.


title: Exceptional flexibility in the sequence requirements for coronavirus small envelope protein function.

text: The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To investigate the role of E protein in the whole virus, we previously generated E gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth and produced aberrantly assembled virions. Surprisingly, however, we were also able to isolate a viable MHV mutant (DeltaE) in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, were deleted. We have now constructed an E knockout mutant that confirms that the highly defective phenotype of the DeltaE mutant is due to loss of the E gene. Additionally, we have created substitution mutants in which the MHV E gene was replaced by heterologous E genes from viruses spanning all three groups of the coronavirus family. Group 2 and 3 E proteins were readily exchangeable for that of MHV. However, the E protein of a group 1 coronavirus, transmissible gastroenteritis virus, became functional in MHV only after acquisition of particular mutations. Our results show that proteins encompassing a remarkably diverse range of primary amino acid sequences can provide E protein function in MHV. These findings suggest that E protein facilitates viral assembly in a manner that does not require E protein to make sequence-specific contacts with M protein.


title: Severe acute respiratory syndrome in children.

text: BACKGROUND Severe acute respiratory syndrome (SARS) is a febrile, respiratory tract illness caused by infection with the newly identified SARS-associated coronavirus. A notable feature of the 2003 global SARS outbreak was the relative paucity of cases reported among children. We reviewed the epidemiologic and clinical features of SARS in children and discuss implications of these findings for diagnosis, treatment and prevention of SARS. METHODS We performed a literature search to identify reports of pediatric (younger than 18 years of age) patients meeting the World Health Organization case definitions for SARS and abstracted relevant clinical and epidemiologic information. RESULTS We identified 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore. Among laboratory-confirmed and probable SARS cases, the most common symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had radiographic abnormalities. The clinical presentation of SARS in patients older than 12 years of age was similar to that in adults. However, patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS, and at 6 months after illness only mild residual changes were reported in exercise tolerance and pulmonary function. There is only 1 published report of transmission of SARS virus from a pediatric patient. CONCLUSIONS Children and adolescents are susceptible to SARS-associated coronavirus infection, although the clinical course and outcome are more favorable in children younger than 12 years of age compared with adolescents and adults. Transmission of SARS from pediatric patients appears to be uncommon but is possible.


title: Respiratory viruses predisposing to bacterial infections: role of neuraminidase.

text: BACKGROUND AND METHODS Viral-bacterial coinfections in humans are well-documented. Viral infections often lead to bacterial superinfections. In vitro and animal models for influenza, as well as molecular microbiology study of viruses and bacteria, provide an understanding of the mechanisms that explain how respiratory viruses and bacteria combine to cause disease. This article focuses on viral and bacterial combinations, particularly synergism between influenza and Streptococcus pneumoniae. RESULTS Potential mechanisms for synergism between viruses and bacteria include: virus destruction of respiratory epithelium may increase bacterial adhesion; virus-induced immunosuppression may cause bacterial superinfections; and inflammatory response to viral infection may up-regulate expression of molecules that bacteria utilize as receptors. Influenza and parainfluenza viruses possess neuraminidase (NA) activity, which appears to increase bacterial adherence after viral preincubation. Experimental studies demonstrate that viral NA exposes pneumococcal receptors on host cells by removing terminal sialic acids. Other studies show that inhibition of viral NA activity reduces adherence and invasion of S. pneumoniae, independently of effects on viral replication. Clinical studies reveal that influenza vaccination reduces the incidence of secondary bacterial respiratory tract infections. CONCLUSIONS Detection of viral factors (e.g. high NA activity) that increase the likely potential of epidemic/pandemic influenza strains for causing morbidity and mortality from secondary bacterial infections provides new possibilities for intervention. Additional study is needed to identify the mechanisms for the development of bacterial complications after infections with respiratory syncytial virus and other important respiratory viruses that lack NA activity. Prevention of bacterial superinfection is likely to depend on effective antiviral measures.


title: Genomic and bioinformatics analysis of HAdV-4, a human adenovirus causing acute respiratory disease: implications for gene therapy and vaccine vector development.

text: Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.


SARS in Hong Kong.


title: A novel sutureless colonic anastomosis with self-gripping mesh: an experimental model.

text: INTRODUCTION Anastomotic leakage is one of the most feared complications of colorectal surgery. High morbidity and mortality rates are related to this complication and several studies had been performed to test new techniques which are suggested to reduce leakage rates. The aim of our study was to evaluate the safety and effectiveness of a novel technique sutureless anastomosis with self-gripping mesh in an animal model by examining wound healing process in anastomosis. METHODS In this study sixteen Norwegian Wistar Albino female rats were used. The rats' weights ranged from 250 to 300 g. The rats were divided into control and study groups. The control group underwent a colocolic anastomosis using the conventional method of hand-sewing with single-layer interrupted nonabsorbable sutures. The study group underwent a colocolic anastomosis using self-gripping mesh without sutures. These rats were sacrificed on the 10th postoperative day. The sample pieces obtained from the groups were subjected to anastomotic bursting pressure tests, to a test for hydroxyproline levels in the tissue and to histopathological examinations. The tissue was evaluated in terms of quantity of inflammatory cells, fibroblasts, neovascularization level and collagen content and classified according to the Ehrlich-Hunt model. Statistical analysis was done by using Mann-Whitney U test. RESULTS The burst pressure mean ± range of control and study groups were 162 ± 78 and 123 ± 35, respectively (P = 0.049). The mean peritoneal adhesion grades were 3.2 ± 0.7 in the study group and 2.3 ± 0.7 in the control group (P = 0.036). The operative time was significantly shorter in the study group. The difference between the groups by mean of hydroxyproline levels was found to be significant (P = 0.001). According to histopathological examinations by means of the Ehrlich-Hunt model, the fibroblast activation and collagen fiber ratio were higher in the study group and the difference between these measurements was statistically significant (P = 0.006; P = 0.028). CONCLUSION This study showed that use of self-gripping meshes for colocolic anastomosis in rats is a safe and feasible method. It is suggested that the most important advantage of this technique is the shorter operative time.


Chasing hyponatraemia in preterm infants.


title: Imported case of MERS-CoV infection identified in China, May 2015: detection and lesson learned.

text: At the end of May 2015, an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was confirmed in China. The patient is in a stable condition and is still undergoing treatment. In this report, we summarise the preliminary findings for this imported case and the results of contact tracing. We identified 78 close contacts and after 14 days of monitoring and isolation, none of the contacts presented symptoms and all tested negative for MERS-CoV.


title: Antigenic variations among calf diarrhea coronaviruses by immunodiffusion and counterimmunoelectrophoresis.

text: The antigenic relationship among five bovine coronavirus isolates was studied using the counterimmunoelectrophoresis (CIE) and immunodiffusion (ID) techniques. By CIE, two precipitating antigens were observed for each coronavirus isolate. One antigen identified as the "M" coronaviral antigen was found to be common to the five isolates while the second antigen identified as the "m" coronaviral antigen differed between the isolates. Considering the later antigen, the isolates studied were placed in two antigenic groups, members of the same group being indistinguishable for the two antigens. By ID, reactions of partial identity were noted between viruses of the different groups.


title: Development, characterization, and diagnostic applications of monoclonal antibodies against bovine rotavirus.

text: Hybridomas secreting monoclonal antibodies (MAbs) against the Nebraska calf diarrhea strain of bovine rotavirus (BRV) were characterized. Indirect fluorescent-antibody assay, immunodot assay, and immunoprecipitation were used to select hybridomas that produced anti-BRV MAbs. Seven of the MAbs were shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot assay to be reactive with the BRV outer capsid protein, VP7, which has a molecular mass of 37.5 kDa. None of the seven MAbs were reactive with canine rotavirus, bovine coronavirus, or uninfected Madin-Darby bovine kidney cells. Two clones, 8B4 (immunoglobulin G2a [IgG2a]) and 2B11 (IgG1), were found suitable for use in an antigen capture enzyme-linked immunosorbent assay for detecting BRV in bovine fecal samples. Both were subtype A specific (G6 subtype) but did not react with all isolates of BRV group A.


SARS-associated coronavirus quasispecies in individual patients.


title: Quantification of Tomographic Patterns associated with COVID-19 from Chest CT.

text: PURPOSE To present a method that automatically segments and quantifies abnormal CT patterns commonly present in coronavirus disease 2019 (COVID-19), namely ground glass opacities and consolidations. MATERIALS AND METHODS In this retrospective study, the proposed method takes as input a non-contrasted chest CT and segments the lesions, lungs, and lobes in three dimensions, based on a dataset of 9749 chest CT volumes. The method outputs two combined measures of the severity of lung and lobe involvement, quantifying both the extent of COVID-19 abnormalities and presence of high opacities, based on deep learning and deep reinforcement learning. The first measure of (PO, PHO) is global, while the second of (LSS, LHOS) is lobewise. Evaluation of the algorithm is reported on CTs of 200 participants (100 COVID-19 confirmed patients and 100 healthy controls) from institutions from Canada, Europe and the United States collected between 2002-Present (April, 2020). Ground truth is established by manual annotations of lesions, lungs, and lobes. Correlation and regression analyses were performed to compare the prediction to the ground truth. RESULTS Pearson correlation coefficient between method prediction and ground truth for COVID-19 cases was calculated as 0.92 for PO (P < .001), 0.97 for PHO(P < .001), 0.91 for LSS (P < .001), 0.90 for LHOS (P < .001). 98 of 100 healthy controls had a predicted PO of less than 1%, 2 had between 1-2%. Automated processing time to compute the severity scores was 10 seconds per case compared to 30 minutes required for manual annotations. CONCLUSION A new method segments regions of CT abnormalities associated with COVID-19 and computes (PO, PHO), as well as (LSS, LHOS) severity scores.


title: Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV, or SCV), which caused a world-wide epidemic in 2002 and 2003, binds to a receptor, angiotensin-converting enzyme 2 (ACE2), through the receptor-binding domain (RBD) of its envelope (spike, S) glycoprotein. The RBD is very immunogenic; it is a major SCV neutralization determinant and can elicit potent neutralizing antibodies capable of out-competing ACE2. However, the structural basis of RBD immunogenicity, RBD-mediated neutralization, and the role of RBD in entry steps following its binding to ACE2 have not been elucidated. By mimicking immune responses with the use of RBD as an antigen to screen a large human antibody library derived from healthy volunteers, we identified a novel potent cross-reactive SCV-neutralizing monoclonal antibody, m396, which competes with ACE2 for binding to RBD, and determined the crystal structure of the RBD-antibody complex at 2.3-A resolution. The antibody-bound RBD structure is completely defined, revealing two previously unresolved segments (residues 376-381 and 503-512) and a new disulfide bond (between residues 378 and 511). Interestingly, the overall structure of the m396-bound RBD is not significantly different from that of the ACE2-bound RBD. The antibody epitope is dominated by a 10-residue-long protruding beta6-beta7 loop with two putative ACE2-binding hotspot residues (Ile-489 and Tyr-491). These results provide a structural rationale for the function of a major determinant of SCV immunogenicity and neutralization, the development of SCV therapeutics based on the antibody paratope and epitope, and a retrovaccinology approach for the design of anti-SCV vaccines. The available structural information indicates that the SCV entry may not be mediated by ACE2-induced conformational changes in the RBD but may involve other conformational changes or/and yet to be identified coreceptors.


title: Knowledge, Attitude And Practice Of Common Cold And Its Management Among Doctors Of Pakistan.

text: BACKGROUND Antibiotic misuse for upper respiratory tract infections such as the common cold is widespread in clinical practice. Excessive prescription of antibiotics by doctors has resulted in increased antimicrobial resistance. This led to our objective of determining the percentage of doctors in Pakistan prescribing antibiotics for the treatment of common cold and to know about their knowledge in preventing the spread of this disease. METHODS It was a cross-sectional descriptive study, conducted in 9 cities of Pakistan including Rawalpindi, Islamabad, Peshawar, Lahore, Karachi, Faisalabad, Sargodha, Multan and D.G. Khan over a period of 03 months -from October to December, 2013. Questionnaire regarding the disease spread and its treatment was distributed among 300 randomly selected doctors in nine cities of Pakistan from both public and private sector. RESULTS Eighteen percent of the doctors prescribe antibiotics for common cold. Only 113 (37.7%) doctors correctly responded that mean incubation period for common cold was 1-2 days. Two hundred and nine (69.7%) answered correctly that cold weather increases susceptibility to common cold. Only 84 (28%) responded correctly by choosing that regular and frequent hand-washing with good quality soaps was the most effective way to prevent spread of this disease in day-to-day life. CONCLUSIONS Antibiotics are being prescribed for treatment of common cold by a large proportion of doctors. There is insufficient knowledge among our doctors regarding the factors which aggravate or alleviate common cold symptoms as well as the methods by which these infections can be prevented.


title: [Expression, purification and identification of recombinant SARS coronavirus membrane protein].

text: A novel coronavirus (SARS-coronavirus, SARS-CoV) was discovered as the pathogen of the severe acute respiratory syndrome (SARS). According to studies with other coronaviruses, the membrane protein (M protein) is the main structural protein and the recombinant M protein may be useful as an antigen for detecting antibodies against coronavirus and for preparing vaccine. In this work, the M protein of SARS-CoV was expressed in E. coli as fusion protein with maltose binding protein at N-terminus and MxeGyrA intein CBD at C-terminus. The recombinant protein was identified by Western blot and mass spectrometry. The soluble parts of the cell crude extract were then partially purified by MBP affinity chromatography. The purified protein will be used for the studies on M protein's structure and the development of diagnostic method of SARS.


title: Using the Barrel Technique with the LVIS Jr (Low-profile Visualized Intraluminal Support) Stent to Treat a Wide Neck MCA Bifurcation Aneurysm.

text: The treatment of wide-neck bifurcation cerebral aneurysms is challenging especially if at least one of the arteries arise from an obtuse angle. These wide-neck bifurcation aneurysms are difficult to treat with the usual balloon and stent assisted coiling, including Y stenting or double-barrel stent techniques [1, 2]. Other available options include using current devices with the waffle cone or double waffle cone techniques [3, 4]. Novel devices that are in development include intrasaccular devices and the barrel bifurcation vascular reconstruction device (Covidien) [5, 6, 7]. We report the use of a novel barrel technique using the LVIS (low-profile visualized intraluminal support) Jr stent for the treatment of a wide-neck bifurcation aneurysm.


Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions.


title: Viral encephalitis: a review of diagnostic methods and guidelines for management.

text: Viral encephalitis is a medical emergency. The spectrum of brain involvement and the prognosis are dependent mainly on the specific pathogen and the immunological state of the host. Although specific therapy is limited to only several viral agents, correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury in survivors. We searched MEDLINE (National Library of Medicine) for relevant literature from 1966 to May 2004. Review articles and book chapters were also included. Recommendations are based on this literature based on our judgment of the relevance of the references to the subject. Recommendations were reached by consensus. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. Diagnosis should be based on medical history, examination followed by analysis of cerebrospinal fluid for protein and glucose contents, cellular analysis and identification of the pathogen by polymerase chain reaction (PCR) amplification (recommendation level A) and serology (recommendation level B). Neuroimaging, preferably by magnetic resonance imaging, is an essential aspect of evaluation (recommendation level B). Lumbar puncture can follow neuroimaging when immediately available, but if this cannot be obtained at the shortest span of time it should be delayed only in the presence of strict contraindications. Brain biopsy should be reserved only for unusual and diagnostically difficult cases. All encephalitis cases must be hospitalized with an access to intensive care units. Supportive therapy is an important basis of management. Specific, evidence-based, anti-viral therapy, acyclovir, is available for herpes encephalitis (recommendation level A). Acyclovir might also be effective for varicella-zoster virus encephalitis, gancyclovir and foscarnet for cytomegalovirus encephalitis and pleconaril for enterovirus encephalitis (IV class of evidence). Corticosteroids as an adjunct treatment for acute viral encephalitis are not generally considered to be effective and their use is controversial. Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management.


title: Identification, molecular characterization, and experimental transmission of a new hemoplasma isolate from a cat with hemolytic anemia in Switzerland.

text: Recently, there has been a growing interest in hemotropic mycoplasmal species (also known as the hemoplasmas), the causative agents of infectious anemia in several mammalian species. In felids, two different hemoplasma species have been recognized: Mycoplasma haemofelis (formerly Haemobartonella felis) and "Candidatus Mycoplasma haemominutum." Recently developed molecular methods have allowed sensitive and specific identification and quantification of these agents in feline blood samples. In applying these methods to an epidemiological study surveying the Swiss pet cat population for hemoplasma infection, we discovered a third novel and unique feline hemoplasma isolate in a blood sample collected from a cat that had exhibited clinical signs of severe hemolytic anemia. This agent was readily transmitted via intravenous inoculation to two specific-pathogen-free cats. One of these cats was immunocompromised by the administration of methylprednisolone acetate prior to inoculation, and this cat developed severe anemia. The other immunocompetent cat showed a moderate decrease in packed cell volume. Additionally, an increase in red blood cell osmotic fragility was observed. Sequencing of the entire 16S rRNA gene of the new hemoplasma isolate and phylogenetic analysis showed that the isolate was most closely related to two rodent hemotropic mycoplasmal species, M. coccoides and M. haemomuris. A quantitative real-time PCR assay specific for this newly discovered agent was developed, which will be a prerequisite for the diagnosis of infections with the new hemoplasma isolate.


title: Forecast and control of epidemics in a globalized world.

text: The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the geographical spread of epidemics is indeed possible. This model combines a stochastic local infection dynamics among individuals with stochastic transport in a worldwide network, taking into account national and international civil aviation traffic. Our simulations of the severe acute respiratory syndrome outbreak are in surprisingly good agreement with published case reports. We show that the high degree of predictability is caused by the strong heterogeneity of the network. Our model can be used to predict the worldwide spread of future infectious diseases and to identify endangered regions in advance. The performance of different control strategies is analyzed, and our simulations show that a quick and focused reaction is essential to inhibiting the global spread of epidemics.


Coronavirus subgenomic replicons as a mechanism for mRNA amplification.


title: Triaryl pyrazoline compound inhibits flavivirus RNA replication.

text: Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 microM and a compound concentration of >or=300 microM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.


title: Adverse events of stapling in thoracic surgery: relations between an incidence of adverse events and a stapling volume.

text: PURPOSE The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, sometimes adverse events (AEs) of stapling are experienced. The aim of the present study was to retrospectively analyze AEs of stapling in thoracic surgery. METHODS A retrospective multi-institutional review was conducted by the 27 institutions of the Central Japan Lung Cancer Surgery Study Group. Between January 2009 and December 2010, 4495 patients underwent thoracic surgery using mechanical stapling. RESULTS Stapling of various tissues was performed 16403 times. Total number of AEs related to stapling was 126 (0.77%). One hundred and nine events occurred intraoperative and 17 events occurred postoperative. The AE rates ranged from 0% to 1.8%. No relationship was seen between the incidence of AE and a stapling volume of thoracic surgery. CONCLUSION We have investigated intraoperative and postoperative AEs of stapling. Generally, stapling in thoracic surgery was safe. An AE rate of stapling in thoracic surgery is not influenced by the numbers of stapling in institutions.


title: Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study.

text: PURPOSE The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.


title: Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.

text: The novel coronavirus SARS-CoV-2 (Covid-19), spreading from Wuhan, China, is one of the causes of respiratory infections that can spread to other people through respiratory particles, and can cause symptoms such as fever, dry cough, shortness of breath, anorexia, fatigue and sore throat in infected patients. This review summarizes current strategies on the diagnosis. Additionally, treatments, infection prevention and control of the SARS-CoV-2 are addressed. In addition to the respiratory system, this virus can infect the digestive system, the urinary system and the haematological system, which causes to observe the virus in the stool, urine and blood samples in addition to throat sample. The SARS-CoV-2 causes changes in blood cells and factors and makes lung abnormalities in patients, which can be detected by serological, molecular, and radiological techniques by detecting these changes and injuries. Radiological and serological methods are the most preferred among the other methods and the radiological method is the most preferred one which can diagnose the infection quickly and accurately with fewer false-negatives, that can be effective in protecting the patient's life by initiating treatment and preventing the transmission of infection to other people.


title: The immunology of virus infection in asthma.

text: The respiratory tract is commonly infected by a range of viruses with overlapping pathologies. The majority of episodic exacerbations of asthma are associated with viral infection, in particular with rhinovirus infections. Experimental rhinovirus infection in human volunteers provides a useful model of natural virus-induced asthma. The asthmatic airway is characterized by an infiltrate of eosinophils and T-lymphocytes expressing the type 2 cytokines interleukin (IL)-4, IL-5 and IL-13. An effective antiviral immune response requires early viral clearance and appropriate termination of the immune response to minimize associated immunopathology and tissue damage. The antiviral immune response is made up of innate (nonspecific) and specific components, and requires the coordinated actions of many different cell types including neutrophils, macrophages, eosinophils, dendritic cells, epithelial cells, mast cells, natural killer cells and B- and T-lymphocytes. Coordination of this response involves numerous cytokines and chemokines. T-lymphocytes expressing type 1 cytokines including interferon-gamma play a key role. Pre-existing asthmatic inflammation in the lower airway may modify the immune response to viral infection by altering the balance of T-cell cytokine expression from type 1 towards a type 2 in what is always a mixed response. The consequence is delayed viral clearance, persistent virus-induced inflammation and amplification of the allergic inflammation.


Controlling immune response may cut bird flu death rate.


Influenza C virus infection in children, Spain.


title: Neuropathological findings in cats with clinically suspect but histologically unconfirmed feline spongiform encephalopathy.

text: Central nervous system (CNS) tissues from 192 cats with neurological signs were examined histologically, and tissues from 173 of them were later examined immunohistochemically as part of a survey to determine the prevalence of feline spongiform encephalopathy (FSE). One of the cats was from Norway and the others were from Great Britain. The most commonly recorded clinical signs were ataxia, behavioural changes and epilepsy, but none of the cats had histopathological evidence of FSE. The most common organic CNS lesions were non-suppurative encephalomyelitis in 28 per cent, neoplasia in 15 per cent and a heterogeneous group of degenerative encephalopathies in 9 per cent of the cats. A range of minor histological lesions of uncertain significance was also observed. No histological lesions were observed in the tissues of 63 (33 per cent) of the cats. Disease-specific prion protein (PrP(Sc)) was observed in only one of the 173 cats examined by immunohistochemistry.


title: SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF IMIDAZO[2,1- b][1,3,4]THIADIAZOLE DERIVATIVES.

text: In this paper, a series of imidazo[2,l-b][1,3,4]thiadiazoles have been prepared by reacting 2-amino-1,3,4-thiadiazole with various phenacyl bromides in alcohol. The structures of all the derivatives were con- firmed by IR, NMR and mass spectroscopy. All the derivatives have been tested for cytostatic activity against human T-lymphocyte cells (CEM), human cervix carcinoma cells (HeLa), murine leukemia cell line (L1210), and antiviral activity. Among the tested compounds, derivatives 5b, 5c, and 7a were cytostatic between 49-63 mM against Hela and 7g was cytotoxic at 23 mM against L1210 and CEM cell lines. Compounds 5h and 7h emerged as antiviral agents with slight activity against influenza A and B.


title: Plasma-derived proteins in airway defence, disease and repair of epithelial injury.

text: One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.


title: [The Isolation and Identification of Infectious Bronchitis Virus PTFY Strain in Muscovy Ducks].

text: In July 2009, some farms of breeding Muscovy ducks on the peak of egg laying suffered the decrease of hatching rate and the quality of the eggs showing low mortality and no evident respiratory symptoms. The swelling and congestive ovary was visible after autopsy. This study was brought out for the diagnosis of these cases. The virus was isolated and identified by the methods of virus culture in chicken embryo, physical and chemical properties test, hemagglutinin test, NDV (Newcastle diseases Virus) interference test, electron microscope observation, pathogenicity test and the gene sequence analysis. The results indicated the virus showed the characters of inducing dwarf embryo after inocubation, the sensibility to lipid solvent and the hemagglutination capacity after pancreatic enzyme treatment, the typical morphology of coronavirus, the interference to NDV replication and the homology among 84.7% - 99% of the particial N gene sequences to the reference IBV (Avian infectious bronchitis virus) strains. The strain was identified as IBV isolate and this study confirmed the pathogenicity of IBV to Muscovy ducks.


title: Carotid artery intima media thickness, plaque and Framingham cardiovascular score in Asia, Africa/Middle East and Latin America: the PARC-AALA study.

text: OBJECTIVE The PARC-AALA (Paroi artérielle et Risque Cardiovasculaire in Asia Africa/ Middle East and Latin America) study was designed to evaluate the correlation between intima-media thickness of the common carotid artery (CCAIMT), carotid plaque and absolute cardiovascular risk in a multi-ethnic population. METHODS An international, cross-sectional, study including 79 centres from 21 countries in Asia, Africa, the Middle East and Latin America. Two thousand three hundred and twenty-eight subjects, meeting all inclusion criteria, were stratified by risk factors groups (no modifiable factor or at least both uncontrolled hypertension and hypercholesterolemia). CCAIMT, presence of plaque and cardiovascular risk factors were assessed for each individual. RESULTS Some intergeographical characteristics in demographics, and risk factors were found accompanying early atherosclerosis marker differences. In Asia where the subjects were at lower risk, the mean CCAIMT was 4% lower than in Africa/Middle East and Latin America. On multiple linear regression analysis CCAIMT and carotid plaque were independently associated with increased Framingham cardiovascular score (FCS) without heterogeneity across geographic regions. CCAIMT and carotid plaque explained roughly 20% of the FCS in both genders. CONCLUSION The PARC-AALA study confirms the correlation between CCAIMT and FCS in three different populations. Intima-media thickness (IMT) and plaque evaluation may represent a complementary predictive tool for detection of cardiovascular disease in individuals.


title: Renal denervation: a new therapeutic approach for resistant hypertension.

text: OBJECTIVE To review the advances in studies on renal denervation. DATA SOURCES References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. STUDY SELECTION Articles with keywords "renal denervation" and "resistant hypertension" were selected. RESULTS Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. CONCLUSIONS Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.


title: Biological invasions: recommendations for U.S. policy and management.

text: The Ecological Society of America has evaluated current U.S. national policies and practices on biological invasions in light of current scientific knowledge. Invasions by harmful nonnative species are increasing in number and area affected; the damages to ecosystems, economic activity, and human welfare are accumulating. Without improved strategies based on recent scientific advances and increased investments to counter invasions, harm from invasive species is likely to accelerate. Federal leadership, with the cooperation of state and local governments, is required to increase the effectiveness of prevention of invasions, detect and respond quickly to new potentially harmful invasions, control and slow the spread of existing invasions, and provide a national center to ensure that these efforts are coordinated and cost effective. Specifically, the Ecological Society of America recommends that the federal government take the following six actions: (1) Use new information and practices to better manage commercial and other pathways to reduce the transport and release of potentially harmful species; (2) Adopt more quantitative procedures for risk analysis and apply them to every species proposed for importation into the country; (3) Use new cost-effective diagnostic technologies to increase active surveillance and sharing of information about invasive species so that responses to new invasions can be more rapid and effective; (4) Create new legal authority and provide emergency funding to support rapid responses to emerging invasions; (5) Provide funding and incentives for cost-effective programs to slow the spread of existing invasive species in order to protect still uninvaded ecosystems, social and industrial infrastructure, and human welfare; and (6) Establish a National Center for Invasive Species Management (under the existing National Invasive Species Council) to coordinate and lead improvements in federal, state, and international policies on invasive species. Recent scientific and technical advances provide a sound basis for more cost-effective national responses to invasive species. Greater investments in improved technology and management practices would be more than repaid by reduced damages from current and future invasive species. The Ecological Society of America is committed to assist all levels of government and provide scientific advice to improve all aspects of invasive-species management.


title: Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes.

text: Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.


COVID-19 Teaches Hard Lessons.


title: Onyx Embolization as Single Rescue Treatment for Ruptured Abdominal Aortic Aneurysm After EVAR.

text: A 76-year-old man who had undergone endovascular repair for an infrarenal aortic aneurysm, presented with a late type Ia endoleak 3 years after his operation. Deployment of an aortic cuff did not achieve a better seal at the proximal neck, and the aneurysm developed a rupture. We successfully treated the ruptured aneurysm using transcatheter Onyx embolization only. At 6-month and 1-year follow-ups with contrast-enhanced duplex scanning, no endoleak was seen and sac shrinkage was observed. Onyx is a relatively new liquid embolic agent that is slowly transformed into a solid state by contact with blood. Owing to this unique characteristic, Onyx embolization can be a useful technique for stopping bleeding from an aneurysm in an emergency situation. This is a unique case of the use of an embolization agent in the treatment of aortic aneurysm rupture.


title: Sensitivity of SARS/MERS CoV to interferons and other drugs based on achievable serum concentrations in humans.

text: A novel coronavirus (MERS-CoV) related to SARS-CoV recently emerged in the Middle East causing more than 400 deaths with a mortality rate of about 30%, much higher than SARS-CoV. Both viruses target epithelial cells in the respiratory tract, although utilizing different cellular receptors. Because of the sporadic nature of the MERS outbreak and difficulty in collecting randomized, controlled clinical data, the objective of this review was to focus on published in vitro and in vivo drug sensitivity data using both cell lines and available animal models of SARS/MERS CoV infection. Determination of drug activity was based on achievable serum levels in humans relative to in vitro IC50 (50% inhibitory concentration) or EC50 (50% effective concentration) drug concentrations. The most active drugs against SARS/MERS CoV at clinically achievable serum levels were type I interferons and a TLR3 agonist, interferon inducer/activator.


title: Novel 2019 coronavirus SARS-CoV-2 (COVID-19): An updated overview for emergency clinicians

text: The novel coronavirus, COVID-19, has quickly become a worldwide threat to health, travel, and commerce. This overview analyzes the best information from the early research, including epidemiologic and demographic features from SARS-CoV-1 and MERS-CoV viruses; lessons learned from the experience of an emergency physician in Northern Italy, where the outbreak has devastated the healthcare system; evidence on transmission and prevention through safe use of PPE; evidence and advice on SARS-CoV-2 testing and co-infection; management options; airway management options; steps for rapid sequence intubation in the ED and managing disaster ventilation; and information on managing pediatric and pregnant patients.


title: Structural requirements for multimerization of the pathogen receptor dendritic cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface.

text: The myeloid C-type lectin dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN, CD209) recognizes oligosaccharide ligands on clinically relevant pathogens (HIV, Mycobacterium, and Aspergillus). Alternative splicing and genomic polymorphism generate DC-SIGN mRNA variants, which have been detected at sites of pathogen entrance and transmission. We present evidence that DC-SIGN neck variants are expressed on dendritic and myeloid cells at the RNA and protein levels. Structural analysis revealed that multimerization of DC-SIGN within a cellular context depends on the lectin domain and the number and arrangement of the repeats within the neck region, whose glycosylation negatively affects oligomer formation. Naturally occurring DC-SIGN neck variants differ in multimerization competence in the cell membrane, exhibit altered sugar binding ability, and retain pathogen-interacting capacity, implying that pathogen-induced cluster formation predominates over the basal multimerization capability. Analysis of DC-SIGN neck polymorphisms indicated that the number of allelic variants is higher than previously thought and that multimerization of the prototypic molecule is modulated in the presence of allelic variants with a different neck structure. Our results demonstrate that the presence of allelic variants or a high level of expression of neck domain splicing isoforms might influence the presence and stability of DC-SIGN multimers on the cell surface, thus providing a molecular explanation for the correlation between DC-SIGN polymorphisms and altered susceptibility to HIV-1 and other pathogens.


Babesiosis in Fairfield County, Connecticut.


title: Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.

text: Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which AdvaxTM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either AdvaxTM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with AdvaxTM was similar to Imject Alum. Overall, RSV vaccine formulated with AdvaxTM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared to unvaccinated mice.


Hepatitis A: a Kupffer cell disease?


title: Identification of a bovine coronavirus packaging signal.

text: A region of the bovine coronavirus (BCV) genome that functions as a packaging signal has been cloned. The 291-nucleotide clone shares 72% homology with the region of mouse hepatitis coronavirus (MHV) gene 1b that contains the packaging signal. RNA transcripts were packaged into both BCV and MHV virions when the cloned region was appended to a noncoronavirus RNA. This is the first identification of a BCV packaging signal. The data demonstrate that the BCV genome contains a sequence that is conserved at both the sequence and functional levels, thus broadening our insight into coronavirus packaging.


title: Coronavirus-associated epizootic catarrhal enteritis in ferrets.

text: OBJECTIVE To characterize clinical signs and lesions and identify the etiologic agent associated with epizootic catarrhal enteritis in domestic ferrets. DESIGN Cross-sectional study. ANIMALS 119 ferrets with epizootic diarrhea of presumed viral cause and 5 control ferrets. PROCEDURE Clinical records and biopsy or necropsy specimens of ferrets with presumed epizootic catarrhal enteritis were reviewed. Immunohistochemical staining for coronavirus antigen was performed on paraffin-embedded tissues from approximately 10% of affected ferrets to identify viral antigen and determine its distribution. Transmission electron microscopy was performed on fecal samples and sections of jejunum. Virus isolation studies as well as immunofluorescent tests for other similar viruses were performed. RESULTS Characteristic microscopic lesions consistent with intestinal coronavirus infection (vacuolar degeneration and necrosis of villus enterocytes; villus atrophy, fusion, and blunting; and lymphocytic enteritis) were consistently detected in affected ferrets. Coronavirus particles were identified in feces and jejunal enterocytes by use of transmission electron microscopy. Immunohistochemical staining of jejunal sections revealed coronavirus antigens. Antigen staining was not detected in healthy ferrets or ferrets with other gastrointestinal tract diseases. Virus isolation was unsuccessful, and other similar viruses were not detected. CONCLUSIONS AND CLINICAL RELEVANCE Results strongly implicate a coronavirus as the causative agent of epizootic catarrhal enteritis in ferrets. Diagnosis may be made on the basis of a combination of historical, clinical, and microscopic findings.


title: Topological and functional analysis of epitopes on the S(E2) and HE(E3) glycoproteins of bovine enteric coronavirus.

text: Monoclonal antibodies (Mabs) were selected which reacted with bovine enteric coronavirus S and HE. Mabs to S were used to identify 2 cleavage products of S, S/gp105 and S/gp90. Monoclonals to S/gp105 and HE neutralised the virus; only Mabs to the latter inhibited haemagglutination and acetyl-esterase activity. Topological distribution of epitopes was studied on these 3 glycoproteins by means of competition binding experiments. Two independent epitopes were characterised on HE, 4 on S/gp105, and 2 on S/gp90. Neutralising Mabs defined one major site on both S/gp105 and HE; however a minor neutralisation epitope was also delineated on S/gp105. Functional mapping using neutralisation-resistant mutants confirmed the topological distribution of epitopes on S/gp105.


title: A highly divergent picornavirus in a marine mammal.

text: Nucleic acids from an unidentified virus from ringed seals (Phoca hispida) were amplified using sequence-independent PCR, subcloned, and then sequenced. The full genome of a novel RNA virus was derived, identifying the first sequence-confirmed picornavirus in a marine mammal. The phylogenetic position of the tentatively named seal picornavirus 1 (SePV-1) as an outlier to the grouping of parechoviruses was found consistently in alignable regions of the genome. A mean protein sequence identity of only 19.3 to 30.0% was found between the 3D polymerase gene sequence of SePV-1 and those of other picornaviruses. The predicted secondary structure of the short 506-base 5'-untranslated region showed some attributes of a type IVB internal ribosome entry site, and the polyprotein lacked an apparent L peptide, both properties associated with the Parechovirus genus. The presence of two SePV-1 2A genes and of the canonical sequence required for cotranslational cleavage resembled the genetic organization of Ljungan virus. Minor genetic variants were detected in culture supernatants derived from 8 of 108 (7.4%) seals collected in 2000 to 2002, indicating a high prevalence of SePV-1 in this hunted seal population. The high level of genetic divergence of SePV-1 compared to other picornaviruses and its mix of characteristics relative to its closest relatives support the provisional classification of SePV-1 as the prototype for a new genus in the family Picornaviridae.


title: We did the right thing: an intervention analysis approach to modeling intervened SARS propagation in Singapore.

text: In this paper, we adopt the Intervention Analysis approach to model an intervened natural process, i.e., propagation of the severe acute respiratory syndrome (SARS) in Singapore, which is affected not only by its own evolutionary history but also by the control measures taken. Using this model, the propagation trend of the epidemic and the effects of different control measures on the outcomes of this epidemic can be simulated and quantitatively analyzed. Based on the model, we have performed an evaluation and sensitivity analysis of the Singapore government's responses to this epidemic. Preliminary results have shown that the control measures taken are effective in controlling the outbreak.


High recombination and mutation rates in mouse hepatitis virus suggest that coronaviruses may be potentially important emerging viruses.


title: Diagnosis of suspected hypovitaminosis A using magnetic resonance imaging in African lions (Panthera leo).

text: Vitamin A deficiency is described in captive lions. Ante mortem diagnosis can either be made by serum analysis or liver biopsy, both of which may be problematic. This study utilised magnetic resonance imaging to identify vitamin A deficiency in lions with relatively mild clinical signs, which could otherwise be attributed to numerous other neurological conditions. Magnetic resonance imaging is a non-invasive, reliable diagnostic tool to demonstrate pathology typically associated with this condition. To accommodate varying lion ages and sizes, a number of cranium and brain measurements were compared with that of the maximum diameter of the occular vitreous humor. Occular ratios of the tentorium cerebelli osseum and occipital bone were most reliable in diagnosing the thickened osseous structures characteristic of hypovitaminosis A. The ratio of maximum:minimum dorsoventral diameter of the C1 spinal cord was also of value.


title: The impact of severe acute respiratory syndrome on the use of and requirements for filters in Canada.

text: This article begins with a brief look at the epidemiology of SARS in Canada and then discusses barrier use and potential containment strategies that could be applied to the respiratory equipment and supportive procedures that have been implicated in the spread of SARS or other respiratory infections. The article ends with a discussion of how practice and regulations have changed in Canada since SARS and some suggestions on how practice or regulations could further improve.


title: Medical social work practice and SARS in Singapore.

text: This article reports on the findings of a qualitative study exploring the impact of SARS on social work practice in five different hospitals in Singapore. The study sought to examine the range of interventions adopted by 28 medical social workers and the theoretical orientations underpinning them. The findings discussed include the impact of infection control practices on social work intervention, the range of interventions undertaken, respondents' reflections and self-awareness, the role of values and ethics, creativity and training, and their recommendations for future emergencies. While the findings of the study relate specifically to hospital social work practice, the crisis and trauma nature of the work makes it applicable to a broader range of practice in these areas and a range of populations. The findings from this study could also inform the development of training programs for social work and other clinical health workers, and emergency management planning.


title: Occupational tuberculosis: a review of the literature and the local situation.

text: OBJECTIVE To review the risks and control of occupation-related tuberculosis. DATA SOURCES Statutory notification data, local tuberculosis programme data, and census data were reviewed. Literature search of PubMed was performed up to December 2005. STUDY SELECTION Original and major review articles related to tuberculosis among health care workers and guidelines for prevention were reviewed. DATA EXTRACTION Relevant data were extracted from our literature review and local sources. DATA SYNTHESIS Earlier experimental data demonstrated an airborne spread of tuberculosis and a steady state mathematical model for quantification of the transmission risk. In the post-chemotherapy era in developed countries, few studies demonstrated an occupational risk of tuberculin conversion outside of outbreak settings, and few studies were able to conclusively demonstrate an increased risk of active tuberculosis among health care workers. In countries with limited resource, the situation may be different, with a higher tuberculosis incidence among health care workers. Local tuberculosis programme and notification data from the Labour Department did not show an increased risk of active tuberculosis among health care workers. Although administrative control, engineering control, and personal protection are widely accepted control measures, it is difficult to quantify their cost-effectiveness. CONCLUSIONS Although an increased liability to tuberculosis among health care workers is expected due to the concentration of infectious patients in their environment, prompt diagnosis and initiation of treatment may minimise the risk. A high background rate of disease and possible healthy worker effect may make it difficult to pick up a small risk differential. With the ongoing threat of a nosocomial outbreak, continuing vigilance is called for.


[Ⅲ.Therapeutic Strategy for Relapsed/Refractory Multiple Myeloma-The Logic and Practice].


Detection of SARS coronavirus in plasma by real-time RT-PCR.


title: Ochratoxin A in corn and wheat: geographical association with endemic nephropathy.

text: AIM To determine the presence and concentration of ochratoxin A in wheat and corn from Slavonski Brod surroundings, the area of endemic nephropathy allegedly caused by ochratoxin. METHODS Thin-layer chromatography was used to determine ochratoxin A concentrations in 92 wheat and 51 corn samples from the surroundings of Slavonski Brod, Osijek, Hrvatsko Zagorje, Istria, and Celje (Slovenia). RESULTS Ochratoxin A was present in 74 of 92 (75.8%) wheat samples and 17 of 51 (33.3%) corn samples, in a concentration range of 0.02-160.00 mg/kg in wheat and 0.02-40.00 mg/kg in corn. Wheat samples from the Slavonski Brod surroundings contained the highest level of ochratoxin A (38.8 +/- 27.2 mg/kg), followed by Osijek (8.7 +/- 8.3 mg/kg). Ochratoxin A levels in the wheat from Hrvatsko Zagorje, Istria, and Celje were considerably lower (2.1 +/- 1.5, 1.3 +/- 2.6 and 0.2 +/- 0.5 mg/kg, respectively). Wheat samples from Slavonski Brod significantly differed from all other sample groups (p < 0.001), and wheat samples from Osijek differed from those from Hrvatsko Zagorje, Istria, and Celje (p < 0.001, p = 0.003, p < 0.001, respectively). Ochratoxin A level was the highest in the corn samples from the Slavonski Brod surroundings (20.0 +/- 14.8 mg/kg) and considerably lower in samples from Osijek, Celje, Hrvatsko Zagorje, and Istria (0.8 +/- 1.4, 0.7 +/- 1.9, 0.4 +/- 0.4, and 0.4 +/- 0.8 mg/kg, respectively). A statistically significant difference was also observed between the Slavonski Brod samples and all other corn samples (p < 0.001). CONCLUSION Irrespective of the real association between ochratoxin A and endemic nephropathy, our data clearly demonstrate their geographical overlap.


title: The human microbiome in multiple sclerosis: pathogenic or protective constituents?

text: The human microbiome is comprised of commensal and pathogenic microorganisms, which exert diverse effects in close proximity to the site of intection as well as in remote tissues through immune-mediated mechanisms. Multiple infectious agents have been implicated in the pathogenesis of multiple sclerosis (MS) with variable findings depending on the agent, techniques, and disease phenotype. Herein, the contributions of individual infectious agents to MS and their effects on the immune and nervous systems are reviewed, focusing on herpes viruses, coronaviruses, retroviruses, and synchronic infections. While infectious agents are often assumed to be pathogenic, their effects might also be beneficial to the host in the long-term, depending on age and the type of immunogen/pathogen exposure, as proposed by the hygiene hypothesis. The human microbiome has potential impact on future diagnostic and therapeutic issues in MS.


title: From SARS to H7N9: the mechanism of responding to emerging communicable diseases has made great progress in China.

text: The outbreak of severe acute respiratory syndrome (SARS) in 2003 indicated that China's existing former mechanism for emergency management was very vulnerable. The Chinese Government has since established a new mechanism for responding to emerging communicable diseases. This paper examined the current status of and developments in China's response to emerging communicable diseases from the outbreak of SARS in 2003 to the outbreak of H7N9 virus infection in 2013. Results indicated that the current mechanism for emergency responses to emerging communicable diseases in China has made great achievements in terms of command and decision-making, organization and collaboration, monitoring and early warning systems, protection, and international communication and cooperation. This mechanism for responding to emerging communicable diseases allowed China to successfully deal with outbreaks of the H5N1 bird flu, H1N1 flu, and H7N9 bird flu. However, a better coordination system, a more complete Office of Responses to Public Health Emergencies, administrative responsibility and error correction, better personnel training, and government responsibility may help to improve the response to emerging communicable diseases. Such improvements are eagerly anticipated.


Hemoglobin in samples with leukocytosis can be measured on ABL 700 series blood gas analyzers.


title: Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A.

text: Dengue fever is an important emerging public health concern, with several million viral infections occurring annually, for which no effective therapy currently exists. The NS3 protein from Dengue virus is a multifunctional protein of 69 kDa, endowed with protease, helicase, and nucleoside 5'-triphosphatase (NTPase) activities. Thus, NS3 plays an important role in viral replication and represents a very interesting target for the development of specific antiviral inhibitors. We present the structure of an enzymatically active fragment of the Dengue virus NTPase/helicase catalytic domain to 2.4 A resolution. The structure is composed of three domains, displays an asymmetric distribution of charges on its surface, and contains a tunnel large enough to accommodate single-stranded RNA. Its C-terminal domain adopts a new fold compared to the NS3 helicase of hepatitis C virus, which has interesting implications for the evolution of the Flaviviridae replication complex. A bound sulfate ion reveals residues involved in the metal-dependent NTPase catalytic mechanism. Comparison with the NS3 hepatitis C virus helicase complexed to single-stranded DNA would place the 3' single-stranded tail of a nucleic acid duplex in the tunnel that runs across the basic face of the protein. A possible model for the unwinding mechanism is proposed.


title: Virtual screening of HIV-1 protease inhibitors against human cytomegalovirus protease using docking and molecular dynamics.

text: The clearance of cytomegalovirus viraemia in HIV-1-infected patients may partly result from the inhibition of cytomegalovirus protease by HIV-1 protease inhibitors contained in highly active antiretroviral therapy. We used a computational method to calculate the binding affinity of six HIV-1 protease inhibitors to cytomegalovirus protease based on its X-ray crystallography structure. The calculations showed that amprenavir and indinavir occupy the substrate-binding site of the cytomegalovirus protease with high affinity, and may be implicated in alleviating cytomegalovirus infection.


title: ASPS clinical practice guideline summary on reduction mammaplasty.

text: In May of 2011, the Executive Committee of the American Society of Plastic Surgeons approved an evidence-based guideline on reduction mammaplasty developed by the American Society of Plastic Surgeons Health Policy Committee. The guideline addresses six clinical questions: procedural efficacy as noted by relief of symptoms, resection weight, the impact of body mass index on surgical complications, use of prophylactic antibiotics, use of drains, and effect on quality of life. The evidence indicates that resection volume is not correlated directly to the degree of postoperative symptom relief. Increased breast resection weight may increase the risks of complication. The evidence is inconclusive on whether increased body mass index is associated with increased risk of complications. Perioperative antibiotics may reduce the risk of infection associated with reduction mammaplasty, and in standard reduction mammaplasty procedures without liposuction, the use of drains is not beneficial. Reduction mammaplasty has been shown to improve quality of life.


title: [A single-center prospective study of viral infection in community-acquired pneumonia in adults].

text: From July, 2008 to March, 2009, 125 adults with community-acquired pneumonia (CAP) who were admitted to our hospital were retrospectively investigated to elucidate the characteristics of viral infection in adult CAP in Japan. Nasopharyngeal swabs for real-time polymerase chain reaction for 7 types of influenza virus, rhinovirus, respiratory synctial virus, human metapneumovirus, parainfluenza virus, coronavirus, and enterovirus were obtained. Diagnoses of viral infections were established according to positive results in real-time polymerase chain reaction and influenza rapid diagnostic testing, and based on a fourfold increase in antibody titer of influenza virus antibody in paired sera. Overall, a pathogen was identified in 74 patients (59.8%). Of these pathogens, 47 (37.6%) were bacterial, 17 (13.6%) were viral, and 10 (8.0%) were mixed virus and bacterial infection. Influenza virus (n = 12; 9.6%), rhinovirus (n = 8; 6.4%), respiratory syncytial virus (n = 8; 6.4%), and parainfluenza virus (n = 6; 4.8%) were detected. Adenovirus, coronavirus or enterovirus was not detected. Sore throat was more frequently found in patients with viral pneumonia than in those with non-viral pneumonia. Higher age and pneumococcal pneumonia were factors which contributed to severity in the present cases. It is difficult to distinguish viral pneumonia from non-viral pneumonia by clinical findings, and there were few clinically meaningful differences in presentation and severity, and no differences in severity or outcomes according to either the presence or absence of viral infection. Further studies are needed to clarify the possible significance of viral infection in CAP.


title: [Clinical analysis of 190 cases of outbreak with atypical pneumonia in Guangzhou in spring, 2003].

text: OBJECTIVE To study methods of diagnosis and treatment for atypical pneumonia (Severe Acute Respiratory Syndrome), outbreak of the illness in Guangzhou during Jan. - Mar., 2003. METHODS 190 cases with atypical pneumonia were analyzed, and the cases were admitted in Guangzhou municipal First Hospital and Guangzhou municipal Eighth Hospital. RESULTS Patients were infected by close quarters contacting each other. All patients manifest high fever, and accompany by dyspnea, cough, palpitate, weakness, headache and swirl. Other 46 cases were accompanied by diarrhea. Most of patients, manifestation of lungs was negative. Chest X-ray, shadow of lungs were light in beginning, and change to severity slowly or suddenly during 5 - 10 days. Of these cases, 36 cases develop to ARDS and 11 cases died with severity ARDS. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid was required that can control deprivation of the disease when toxicosis symptom of patients was severity and shadow of lungs diffuse more and more. CONCLUSION Infectivity of the illness is evidence and spread by airway. Using general antibiotic was of no effect for the illness. Continual positive airway pressure (CPAP) and glucocorticoid are effective for control of the disease.


title: Partial passive protection with two monoclonal antibodies and frequency of feeding of hyperimmune anti-transmissible gastroenteritis virus (TGEV) serum for protection of three-day-old piglets from a TGEV challenge infection.

text: Passive protection experiments were conducted to determine the frequency and amounts of hyperimmune antiserum needed to block a transmissible gastroenteritis virus (TGEV) challenge infection and to identify monoclonal antibodies that are partially protective against TGEV. Hyperimmune antiserum or monoclonal antibodies were added to milk at each feeding or at selected feedings when the amount of antiserum was reduced. Three-day-old piglets were challenged with virulent virus that had been preincubated with antiserum or monoclonal antibodies. The results indicated that supplementing antiserum every other day was not efficacious for protection. Supplementing even small quantities of hyperimmune antiserum (0.5 ml) at least once a day in most cases was sufficient for piglet survival but did not prevent morbidity. Increasing the amount (>2 ml) and providing antiserum 3 times/day completely blocked the TGEV challenge infection. Two monoclonal antibodies were discovered that also provided passive protection for baby pigs. One monoclonal antibody, 5G1, had a high neutralizing titer, and the other, 6C4, was more effective in neutralizing and binding to virulent TGEV than to attenuated TGEVs. Both of these monoclonal antibodies were partially effective as supplements in milk for passive protection. Furthermore, these monoclonal antibodies were useful for boosting the efficacy of TGEV-neutralizing colostrum, which by itself was ineffective. These results show that other antigenic sites, different from the 4-well characterized epitopes on the S glycoprotein of TGEV, also are important for passive protection.


title: The spike protein of infectious bronchitis virus is retained intracellularly by a tyrosine motif.

text: We have analyzed the intracellular transport of the spike (S) protein of infectious bronchitis virus (IBV), an avian coronavirus. Surface expression was analyzed by immunofluorescence microscopy, by surface biotinylation, and by syncytium formation by S-expressing cells. By applying these methods, the S protein was found to be retained intracellularly. Tyr1143 in the cytoplasmic tail was shown to be a crucial component of the retention signal. Deletion of a dilysine motif that has previously been suggested to function as a retrieval signal did not abolish intracellular retention. Treatment of the S proteins with endoglycosidases did not reveal any differences between the parental and the mutant proteins. Furthermore, all S proteins analyzed were posttranslationally cleaved into the subunits S1 and S2. In coexpression experiments, the S protein was found to colocalize with a Golgi marker. Taken together, these results indicate that the S protein of IBV is retained at a late Golgi compartment. Therefore, this viral surface protein differs from the S proteins of transmissible gastroenteritis virus and severe acute respiratory syndrome coronavirus, which are retained at a pre-Golgi compartment or transported to the cell surface, respectively. The implications of these differences are discussed.


title: Biochemical characterization of exoribonuclease encoded by SARS coronavirus.

text: The nsp14 protein is an exoribonuclease that is encoded by severe acute respiratory syndrome coronavirus (SARS-CoV). We have cloned and expressed the nsp14 protein in Escherichia coli, and characterized the nature and the role(s) of the metal ions in the reaction chemistry. The purified recombinant nsp14 protein digested a 5'-labeled RNA molecule, but failed to digest the RNA substrate that is modified with fluorescein group at the 3'-hydroxyl group, suggesting a 3'-to-5' exoribonuclease activity. The exoribonuclease activity requires Mg2+ as a cofactor. Isothermal titration calorimetry (ITC) analysis indicated a two-metal binding mode for divalent cations by nsp14. Endogenous tryptophan fluorescence and circular dichroism (CD) spectra measurements showed that there was a structural change of nsp14 when binding with metal ions. We propose that the conformational change induced by metal ions may be a prerequisite for catalytic activity by correctly positioning the side chains of the residues located in the active site of the enzyme.