title: Novel antiviral agents: a medicinal plant perspective.

text: Several hundred plant and herb species that have potential as novel antiviral agents have been studied, with surprisingly little overlap. A wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been identified. Some volatile essential oils of commonly used culinary herbs, spices and herbal teas have also exhibited a high level of antiviral activity. However, given the few classes of compounds investigated, most of the pharmacopoeia of compounds in medicinal plants with antiviral activity is still not known. Several of these phytochemicals have complementary and overlapping mechanisms of action, including antiviral effects by either inhibiting the formation of viral DNA or RNA or inhibiting the activity of viral reproduction. Assay methods to determine antiviral activity include multiple-arm trials, randomized crossover studies, and more compromised designs such as nonrandomized crossovers and pre- and post-treatment analyses. Methods are needed to link antiviral efficacy/potency- and laboratory-based research. Nevertheless, the relative success achieved recently using medicinal plant/herb extracts of various species that are capable of acting therapeutically in various viral infections has raised optimism about the future of phyto-antiviral agents. As this review illustrates, there are innumerable potentially useful medicinal plants and herbs waiting to be evaluated and exploited for therapeutic applications against genetically and functionally diverse viruses families such as Retroviridae, Hepadnaviridae and Herpesviridae


title: Inhibition of SARS coronavirus helicase by bismuth complexes.

text: A series of bismuth complexes were synthesized and characterized, and most of them exhibited inhibition against the SARS coronavirus helicase ATPase and duplex-unwinding activities at micromolar concentrations.


docid: ymkvbxux

title: Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries.

text: Many tissues including blood, skin, gut and germ cells are continuously maintained by tissue stem cells. Under certain conditions, however, other organs can undergo repair using stem-cell-like progenitors generated by cell de-differentiation. Cell fates have been broadened experimentally, but mechanisms allowing de-differentiation to a stem cell state are poorly known. Germline stem cells begin to differentiate by forming interconnected germ cell cysts (cystocytes), and under certain conditions male mouse cystocytes have been postulated to revert into functional progenitors. Here we report that four- and eight-cell Drosophila germline cystocytes generated either in second instar larval ovaries or in adults over-producing the BMP4-like stem cell signal Decapentaplegic efficiently convert into single stem-like cells. These de-differentiated cells can develop into functional germline stem cells and support normal fertility. Our results show that cystocytes represent a relatively abundant source of regenerative precursors that might help replenish germ cells after depletion by genotoxic chemicals, radiation or normal ageing. More generally, Drosophila cystocytes now provide a system for studying de-differentiation and its potential as a source of functional stem cells.


docid: wgkpoxra

title: A study of RFID application impacts on medical safety.

text: With the international reform in medical management systems gaining ground worldwide, hospital management has gradually begun to shift its focus from providing expensive medical treatment to improving medical service quality and patient safety. In this study, we discuss the application of Radio Frequency Identification (RFID) and data integrating technology with the medical service, and examine whether or not this technology can enhance medical safety. We also discuss the possible benefits following the application of the RFID system. The findings show that the application of RFID to hospitals can actually generate benefits, which can be further divided into operational structure benefits, users' structure benefits, and organisational and environmental benefits. However, not all these benefits can achieve medical safety. Among them, only the operator and environmental benefits can play such roles. Nevertheless, the application of RFID can bring hospitals towards the integration of technology benefits and improved medical safety.


title: A new nucleotide-composition based fingerprint of SARS-CoV with visualization analysis.

text: It has been observed by conducting an extensive analysis of the two-dimensional cellular automata images of known SARS-CoV genome sequences that the V-shaped cross-lines only exist in some special locations, and hence can be used as a fingerprint to identify the SARS sequences. Such a discovery can be used to rapidly and reliably diagnose SARS coronavirus for both basic research in laboratories and practical application in clinics.


title: Host intraspatial selection of infectious bronchitis virus populations.

text: Arkansas (Ark)-type infectious bronchitis virus (IBV) subpopulations with an S gene sequence distinct from the vaccine predominant consensus were previously found in the upper respiratory tract of chickens within 3 days after inoculation. This finding indicated that a distinct virus subpopulation was rapidly positively selected by the chicken upper respiratory tract. We hypothesized that during host invasion, the replicating IBV population further changes as it confronts the distinct environments of different tissues, leading to selection of the most fit population. We inoculated 15-day-old chickens with 10(4) 50% embryo infective doses of an Ark-type IBV commercial vaccine via the ocular and nasal routes and characterized the sequences of the S1 gene of IBV contained in tear fluid, trachea, and reproductive tract of individual chickens at different times postinoculation. The predominant IBV phenotype contained in the vaccine (before inoculation) became a minor or nondetectable population at all times in all tissues after replication in the majority of the chickens, corroborating our previous findings. Five new predominant populations designated component (C) 1 through C5, showing distinct nonsynonymous changes, i.e., nucleotide changes resulting in different amino acids encoded and thus in a phenotypic change of the predominant virus population, were detected in the tissues or fluids of individual vaccinated chickens. Due to the different biochemical properties of some amino acids that changed in the S1 glycoprotein, we anticipate that phenotypic shift occurred during the invasion process. Significant differences were detected in the incidence of some distinct IBV predominant populations in tissues and fluids; e.g., phenotype C1 showed the highest incidence in the reproductive tract of the chickens, achieving a significant difference versus its incidence in the trachea (P < 0.05). These results indicate for the first time that IBV undergoes intraspatial variation during host invasion, i.e., the dominant genotype/phenotype further changes during host invasion as the microenvironment of distinct tissues exerts selective pressure on the replicating virus population.


title: [Preliminary result on the nosocomial infection of severe acute respiratory syndrome in one hospital of Beijing].

text: OBJECTIVE To study the transmission route of severe acute respiratory syndrome (SARS) nosocomial infection. METHODS Ten identified SARS patients were selected from a general hospital in March. Survey was carried out through a standardized questionnaire provided by Chinese Center for Disease Control and Prevention. Contents of the questionnaire would include: history of contact with SARS patient, route of infection, methods used for protection and so on. RESULTS (1) Distribution os SARS patients were confined to 3 wards: 4, 5, and 6 on the 7, 8, 12, 13 and 14 floors in the west unit of the inpatient building. Most of the inpatients were elderly and having severe original diseases. (2) Index patients were the first generation source of transmission and they infected inpatients and medical staff, making them the second generation. People with latent infection who had close contact with SARS patients might also serve as the possible source of transmission. (3) The major transmission routes were: near distant droplet infection and close contact infection. There was also a clue to the probability of aerosol or droplet nuclei infection through air-conditioning and ventilation system. CONCLUSION Nosocomial infection appeared to be the main characteristic of the SARS epidemic in the early stage of this hospital. Other than close contact and near space airborne transmission of SARS virus, the possibility of long-distance aerosol transmission called for further epidemiological and experimental studies in the future.


title: Four cases with Kawasaki disease and viral infection: aetiology or association.

text: The aetiology of Kawasaki disease has not yet been precisely determined. It has been associated with a variety of bacterial and viral agents. Some viruses including human adenovirus, coronavirus, and parainfluenza virus type 3 have been isolated from patients with Kawasaki disease. Clinical presentation of patients with human coronavirus and adenovirus infections mimics Kawasaki disease. In addition, these viruses may also be detected in Kawasaki disease as a coinfection. In this report, we present four Kawasaki disease patients infected with adenovirus, coronavirus OC43/HKU1 and parainfluenza virus type 3.


title: Results after laparoscopic left anterior transperitoneal submesocolic adrenalectomy for the treatment of pheochromocytoma.

text: AIM Minimally invasive adrenalectomy is the treatment of choice for benign adrenal lesions including pheocromocytoma (PHE) and in selected patients with malignant lesions. The aim of the present study is to evaluate the authors' results after laparoscopic left anterior transperitoneal submesocolic adrenalectomy (LLATSA) for unilateral PHE. MATERIAL OF STUDY This study is a retrospective analysis of prospectively collected data. From 1994 to 2018, 552 patients underwent laparoscopic adrenalectomy (LA). Of these, 34 patients (14 men, 20 women, mean age 52.8 years) underwent LLATSA for PHE. RESULTS Mean operative time was 93.1 ± 44.9 minutes. Conversion to open surgery occurred in two patients due to difficult identification of the anatomy. Intraoperative blood pressure and heart rate instability were observed in four cases, but with no need for conversion. Postoperative morbidity was nil. One American Society of Anesthesiologists (ASA) III patient died on postoperative day 4 from acute myocardial infarction. Mean postoperative hospital stay was 3.8 ± 1.8 days (range 2 - 8). DISCUSSION The main advantage of this approach is the early ligation of the main adrenal vein prior to any gland manipulation. This reduces the risk of catecholamines' spread and consequently the risk of hemodynamic instability. Intraperitoneal dissection is limited and there is no need to mobilize the colon or pancreas, with a lower risk of complications from organ manipulation. CONCLUSIONS LLATSA is feasible and safe for the treatment of PHE. A randomized trial design and a larger cohort of patients would be required to confirm these conclusions. KEY WORDS Adrenal tumors, Adrenal lesions, Laparoscopic adrenalectomy, Pheochromocytoma, Transperitoneal anterior approach, Laparoscopic left anterior transperitoneal submesocolic adrenalectomy (LLATSA).


title: Single-port plus an additional port robotic complete mesocolic excision and intracorporeal anastomosis using a robotic stapler for right-sided colon cancer.

text: The concept of complete mesocolic excision and central vascular ligation for colonic cancer has been recently introduced. The paper describes a technique of right-sided complete mesocolic excision and intracorporeal anastomosis by using a single-port robotic approach with an additional conventional robotic port. We performed a single-port plus an additional port robotic surgery using the Da Vinci Single-Site platform via the Pfannenstiel incision and the wristed robotic instruments via an additional robotic port in the left lower quadrant. The total operative and docking times were 280 and 25 minutes, respectively. The total number of lymph nodes harvested was 36 and the proximal and distal resection margins were 31 and 50 cm, respectively. Single-port plus an additional port robotic surgery for right-sided complete mesocolic excision and intracorporeal anastomosis appears to be feasible and safe. This system can overcome certain limitations of the previous robotic systems and conventional single-port laparoscopic surgery.


docid: zjbrljgn

title: First confirmation of porcine colonic spirochaetosis caused by Brachyspira pilosicoli in Iberian pigs in Spain.


title: Influenza vaccination coverage among health-care personnel --- United States, 2010-11 influenza season.

text: The Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee recommend that all U.S. health-care personnel (HCP) be vaccinated annually against influenza. Nonetheless, influenza vaccination coverage among HCP in the United States has increased slowly over the past decade; during the 2009-10 influenza season, 61.9% of HCP received seasonal influenza vaccination. To update data with estimates from the 2010-11 influenza season, CDC conducted an Internet-based survey of 1,931 HCP who participated in three online survey panels. This report summarizes the results of that survey, which indicated that overall influenza vaccination coverage among HCP was 63.5% during the 2010--11 influenza season, similar to coverage for the 2009-10 season. Among HCP who reported working at a facility where vaccination was required by their employer, 98.1% were vaccinated. Among HCP without such an employer requirement but who were offered vaccination onsite, greater coverage was associated with a personal reminder from the employer to get vaccinated (69.9%), vaccination availability at no cost (67.9%), and vaccination availability for >1 day (68.8%). Influenza vaccination of HCP is needed to protect patients from HCP-transmitted disease. Maximizing influenza vaccination for all HCP is an important part of any comprehensive infection-control program.


title: Proteomics analysis of gastric epithelial AGS cells infected with Epstein-Barr virus.

text: Effects of the Epstein-Barr virus (EBV) on cellular protein expression are essential for viral pathogenesis. To characterize the cellular response to EBV infection, differential proteomes of gastric epithelial AGS cells were analyzed with two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization- time of flight (MALDI-TOF) and liquid chromatography electrospray/ionization ion trap (LC-ESI-IT) mass spectrometry identification. Mass spectrometry identified 9 altered cellular proteins, including 5 up-regulated and 4 down-regulated proteins after EBV infection. Notably 2-DE analysis revealed that EBV infection induced increased expression of heat shock cognate 71 kDa protein, actin cytoplasmic 1, pyridoxine-5'-phosphate oxidase, caspase 9, and t-complex protein 1 subunit alpha. In addition, EBV infection considerably suppressed those cellular proteins of zinc finger protein 2, cyclin-dependent kinase 2, macrophage-capping protein, and growth/ differentiation factor 11. Furthermore, the differential expressional levels of partial proteins (cyclin-dependent kinase 2 and caspase 9) were confirmed by Western blot analysis.Thus, this work effectively provided useful protein-related information to facilitate further investigation of the mechanisms underlying EBV infection and pathogenesis.


docid: vdggvjng

title: IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB), newsletter 1999.


title: Atmospheric movement of microorganisms in clouds of desert dust and implications for human health.

text: Billions of tons of desert dust move through the atmosphere each year. The primary source regions, which include the Sahara and Sahel regions of North Africa and the Gobi and Takla Makan regions of Asia, are capable of dispersing significant quantities of desert dust across the traditionally viewed oceanic barriers. While a considerable amount of research by scientists has addressed atmospheric pathways and aerosol chemistry, very few studies to determine the numbers and types of microorganisms transported within these desert dust clouds and the roles that they may play in human health have been conducted. This review is a summary of the current state of knowledge of desert dust microbiology and the health impact that desert dust and its microbial constituents may have in downwind environments both close to and far from their sources.


title: Substrate specificity of the human coronavirus 229E 3C-like proteinase.

text: Coronavirus gene expression involves proteolytic processing of the gene 1-encoded polyproteins and a key enzyme in this process is the virus-encoded 3C-like proteinase. In this study, we describe the biosynthesis of the human coronavirus 229E 3C-like proteinase in Escherichia coli and the substrate specificity of the purified protein. Using immunofluorescence microscopy, we have also investigated the subcellular localization of the 3C-like proteinase and have found a punctate, perinuclear distribution of the proteinase in virus-infected cells.


title: Identification of viral antigens that induce antibody responses on exposure to coronaviruses.

text: Various techniques were used to look for protective, non-cross-reactive antibodies in the sera of cats exposed to virulent feline infectious peritonitis virus (FIPV). Antibodies reactive with feline enteric coronavirus (FECV) from FIPV-exposed cats were adsorbed by several passages over an FECV-Sepharose column. In an ELISA against FECV and FIPV, the activity against both viruses was removed at the same rate; thus, no FIPV-specific antibodies could be identified. By gel electrophoresis-derived ELISA, the responses of cats surviving FIPV exposure were compared with those of cats succumbing to FIPV exposure to determine whether survival could be correlated with an antibody response against a particular virus protein. Results indicated that both groups responded in the same way to the matrix envelope protein and nucleocapsid proteins. Even though the response to peplomer in each group was weak, the survivor group responded better to this protein. Furthermore, the response of this group to the peplomer protein had the highest correlation with virus neutralization titer.


title: Diagnostic methods for detection of respiratory RNA viruses.

text: This article is a comprehensive description of diagnostic methods for detection of RNA respiratory viruses - respiratory syncytial virus RSV, influenza A and B viruses, parainfluenza 1, 2 and 3 viruses, coronaviruses and rhinoviruses--from cell culture to molecular biology methods. Both patients and medical personnel appear to be at risk of viral infection, specially during the winter season. Moreover, many health care units lack viral diagnostic facilities; therefore, it is essential for medical personnel to have an understanding of the etiology, mechanisms of transmission and of all disposable today diagnostic methods of RNA respiratory viruses. Patients at greatest risk of acquiring nosocomial viral respiratory disease are children, patients with immunodeficiency and patients treated in intensive care.


title: Pharmacists Welcome FDA's Opioids REMS: How Directly Will They Be Affected?

text: Pharmacists will need to become well versed in the FDA's REMS for opioids.


title: Genome instability in BVDV: an examination of the sequence and structural influences on RNA recombination.

text: The cytopathogenic biotype of the pestivirus, bovine viral diarrhea virus, is frequently a product of nonhomologous recombination in the region of the genome encoding the viral NS2-NS3 proteins. The possibility that sequences or structures in this region contributed to a hotspot for RNA recombination was examined. A PCR-based strategy was used to examine viral genomic RNA isolated from tissue samples of cattle persistently infected with the noncytopathogenic biotype of the virus. Analysis of two different regions of the viral genome revealed that recombination was not restricted to particular sequences. Alignment of the genomic sequences undergoing recombination and examination of the predicted secondary structures of the participating RNAs revealed that the dissociation of partial, newly synthesized negative strand RNAs from the positive strand template occurred at many different sites on the molecule. Similarly, it appeared that the reassociation of the RNA polymerase complex with a second positive strand template was frequently influenced by short regions of homology between the nascent RNA strand and open secondary structures in the template molecule.


title: Several rat cell lines share a common defect in their inability to internalize murine coronaviruses efficiently.

text: Infection of rat cells, Schwannoma RN2, hepatoma HTC or myoblast L6, with the murine coronavirus JHM strain results in a persistent infection characterized by the release of virus over an extended period of time with a limited cytopathology. Several stages of the viral replication cycle have been examined in these cells in comparison to those in mouse L2 cells, which are totally permissive to JHM infection. Although the rat cells bound as much virus as the mouse cells. Their ability to internalize it was 40-fold less efficient than the mouse cells. This lower internalization efficiency was not enhanced by pH shock of infected cells, but was by treatment with polyethylene glycol. In all cell types there appeared to be no major differences in the ability of the internalized virus to replicate the viral RNA as determined by slot-blot analysis with a radiolabelled viral cDNA. A similar genetic mechanism appears to be operative in the lines because somatic cell hybrids formed between these lines in various combinations were also deficient in the ability to internalize bound virus. Taken together these results imply that rat cell lines in general share a common deficiency in their inability to internalize murine coronaviruses efficiently. This low efficiency in viral internalization may explain in part the ability of these lines to sustain persistent infections.


title: Epidemiologic survey of bovine diseases in Suriname.

text: A seroepidemiologic survey of cattle diseases was undertaken in Suriname in 1985 to help assess the livestock disease situation in that country. The six diseases covered by the survey were bovine coronavirus infection, bovine rhinotracheitis, bovine virus diarrhea, brucellosis, parainfluenza-3 infection, and respiratory syncytial virus infection. The results indicated relatively low prevalences of these diseases compared to the prevalences found in most developed countries. The reasons for this are uncertain, but the finding suggests that the cattle population in Suriname could lack extensive exposure to these diseases and so could be highly susceptible to them. In addition, the evident need for more thoroughgoing survey data points up the need to establish a continuous animal data health monitoring system in Suriname--as well as in other developing countries where there is a need to objectively assess the livestock disease picture.


title: Pre-oligodendrocytes from adult human CNS.

text: CNS remyelination and functional recovery often occur after experimental demyelination in adult rodents. This has been attributed to the ability of mature oligodendrocytes and/or their precursor cells to divide and regenerate in response to signals in demyelinating lesions. To determine whether oligodendrocyte precursor cells exist in the adult human CNS, we have cultured white matter from patients undergoing partial temporal lobe resection for intractable epilepsy. These cultures contained a population of process-bearing cells that expressed antigens recognized by the O4 monoclonal antibody, but these cells did not express galactocerebroside (a marker for oligodendrocytes), glial fibrillary acidic protein (a marker for astrocytes), or vimentin. Selective elimination of O4-positive (O4+) cells by complement-mediated lysis resulted in inhibition of oligodendrocyte development in vitro. Since O4+ cells have an antigenic phenotype reminiscent of the rat adult oligodendrocyte-type 2 astrocyte progenitor and appear to develop into oligodendrocytes rather than type 2 astrocytes with time in culture, we call them "pre-oligodendrocytes." Neither pre-oligodendrocytes nor oligodendrocytes incorporated 3H-thymidine in response to rat astrocyte-conditioned medium, platelet-derived growth factor, insulin-like growth factor (IGF-1), or basic fibroblast growth factor (bFGF). However, IGF-1 increased the relative abundance of oligodendrocytes to pre-oligodendrocytes, while bFGF had the opposite effect. Cells with the antigenic phenotype of pre-oligodendrocytes were also identified in tissue prints of adult human white matter. We propose that, in human demyelinating diseases such as multiple sclerosis, pre-oligodendrocytes may divide and/or migrate in response to signals present in demyelinated lesions and thus facilitate remyelination.


title: Expression of viral proteins in feline leukemia virus-associated enteritis.

text: Fourteen cases of feline leukemia virus (FeLV)-associated enteritis were immunohistologically examined for the expression of FeLV proteins gp70, p27, and p15E in the jejunum, mesenteric lymph nodes, spleen, and bone marrow. Results were compared with those of FeLV-infected cats without intestinal alterations. Other viral infections and specific bacterial, fungal, and parasitic infections were excluded by standard microbiologic methods, histopathology, immunohistology, and in situ hybridization. In FeLV-associated enteritis, FeLV gp70 and p15E were strongly expressed in intestinal crypt epithelial cells. In contrast, FeLV-positive cats without intestinal alterations showed only faint staining for gp70 and p15E and comparatively strong p27 expression in these cells. Findings suggest a direct relation between FeLV infection and alterations in intestinal crypt epithelial cells that may be attributed to the envelope proteins gp70 and p15E and/or their precursor protein. Distinct similarities to the intestinal changes in the experimentally induced FeLV-feline AIDS syndrome are obvious, suggesting that naturally occurring feline AIDS variants may be responsible for FeLV-associated enteritis.


Toroviruses--members of the coronavirus superfamily?


title: Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors.

text: OBJECTIVE To examine the impact of severe acute respiratory syndrome (SARS) on pulmonary function, exercise capacity, and health-related quality of life (HRQoL) among survivors. METHODS 110 survivors with confirmed SARS were evaluated at the Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset. The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV1), carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire. RESULTS There were 44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index of 23.1 (4.8) kg/m2. Seventy (64%) were healthcare workers. At 6 months 33 subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17 (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15 (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H2O, respectively. The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95% CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the same age groups. There was impairment of HRQoL at 6 months. Patients who required ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who did not. CONCLUSION The exercise capacity and health status of SARS survivors was considerably lower than that of a normal population at 6 months. Significant impairment in surface area for gas exchange was noted in 15.5% of survivors. The functional disability appears out of proportion to the degree of lung function impairment and may be related to additional factors such as muscle deconditioning and steroid myopathy.


title: Barriers and facilitators to establishing a national public health observatory.

text: OBJECTIVE To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO) in Trinidad and Tobago. METHODS A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. RESULTS The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1) provide information to support evidence-informed decision-making for health policy and strategic planning; 2) facilitate data management by establishing data policies, procedures, and standards; 3) increase the use of data by synthesizing and disseminating information; and 4) provide data for benchmarking. However, a number of barriers were identified, including 1) the perception that data collection is not valued; 2) untimely availability of data; 3) limited data synthesis, dissemination, and utilization to inform decision-making; and 4) challenges related to the allocation of human resources and existing information technology. CONCLUSIONS Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean.


title: Oral exposure to diabetes-promoting food or immunomodulators in neonates alters gut cytokines and diabetes.

text: Disease development in diabetes-prone BB rats is modified by the type of diet fed after weaning. The aim of this investigation was to determine whether exposure during the first week of life to antigens from a known diabetes-promoting diet (NIH-07) could modify diabetes incidence and, if so, to what extent this occurs via alterations in systemic T-cell reactivity, gut cytokines, or islet infiltration. Diabetes-prone BB (BBdp) rats were hand-fed twice daily between age 4 and 7 days with vehicle, a hydrolyzed casein (HC)-based infant formula, Pregestimil (PG), PG + cereal-based NIH-07 diet, PG + lipopolysaccharides (LPS) or PG + LPS + silica. After weaning, they were fed either an NIH-07 diet or a semipurified HC (diabetes-retardant) diet until 150 days. In separate studies, 5-day-old BBdp rat pups were administered the aforementioned treatments, and expression of intestinal mRNA for gamma-interferon (IFN-gamma) or transforming growth factor-beta (TGF-beta) was quantified using reverse transcriptase-polymerase chain reaction. The effect of early oral treatment with NIH-07 or PG on systemic T-cell reactivity was evaluated using footpad swelling delayed-type hypersensitivity (DTH) and the popliteal lymph node assay. Oral exposure of neonates to a complex mixture of antigens from the diabetes-promoting diet delayed onset of diabetes (79 vs. 88 days) and prevented disease in approximately one-third of animals. A similar protective effect was seen for neonatal exposure to wheat gluten in animals subsequently weaned onto a semipurified wheat gluten diet. By contrast, LPS-treated neonates displayed more severe insulitis and developed diabetes at an increased rate, which was significantly suppressed by co-administration of silica particles. The protective effect of early exposure to diabetogenic diets was not associated with significant reduction of islet infiltration, and there was no impact on the DTH response to food antigens. However, whereas diabetes-resistant BBc rats developed systemic tolerance to NIH-07 antigens fed chronically, BBdp rats did not. The lack of effect of the early oral antigen regimen on the DTH reaction in the footpad, a classic Th1-mediated reaction, suggests little effect on systemic T-cell reactivity. However, local effects were observed in the small intestine. Oral exposure to diabetes-promoting food antigens or LPS downregulated the Th1 cytokine IFN-gamma and decreased the IFN-gamma/TGF-beta ratio. Thus, oral exposure to diabetes-promoting food antigens and immune modulators in neonates can modify diabetes expression in association with changes in local cytokine balance in the gut.


Middle East respiratory syndrome coronavirus and the upcoming Hajj.


SNMMI COVID-19 Resource Center.


title: A comparison of infection control program resources, activities, and antibiotic resistant organism rates in Canadian acute care hospitals in 1999 and 2005: pre- and post-severe acute respiratory syndrome.

text: INTRODUCTION The Resources for Infection Control in Hospitals (RICH) project assessed infection control programs and rates of antibiotic-resistant organisms (AROs) in Canadian acute care hospitals in 1999. In the meantime, the Severe Acute Respiratory Syndrome (SARS) outbreak and the concern over pandemic influenza have stimulated considerable government and healthcare institutional efforts to improve infection control systems in Canada. METHODS In 2006, a version of the RICH survey similar to the original RICH instrument was mailed to infection control programs in all Canadian acute care hospitals with 80 or more beds. Chi-square, ANOVA, and analysis of covariance analyses tested for differences between the 1999 and 2005 samples for infection control program components and ARO rates. RESULTS 72.3% of Canadian acute care hospitals completed the RICH survey for 1999 and 60.1% for 2005. Hospital size was controlled for in analyses involving AROs and surveillance and control intensity levels. Methicillin-resistant Staphylococcus aureus (MRSA) rates increased from 1999 to 2005 (F = 9.4, P = 0.003). In 2005, the MRSA rate was 5.2 (SD 6.1) per 1,000 admissions and in 1999 was 2.0 (SD 2.9). Clostridium difficile-associated diarrhea (CDAD) rates, trended up from 1999 to 2005 (F = 2.9, P = 0.09). In 2005, the mean CDAD rate was 4.7 (SD 4.3) and in 1999 it was 3.8 (SD 4.3). The proportion of hospitals that reported having new nosocomial Vancomycin-resistant Enterococcus (VRE) cases was greater in 2005 than in 1999 (X = 10.5, P = 0.001). In 1999, 34.5% (40 of 116) hospitals reported having new nosocomial VRE cases and in 2005, 61.0% (64 of 105) reported new cases. Surveillance intensity index scores increased from 61.7 (SD 18.5) in 1999 to 68.1 (SD 15.4) in 2005 (F = 4.1, P = 0.04). Control intensity index scores, trended upwards slightly from 60.8 (SD 14.6) in 1999 to 64.1 (12.2) in 2005 (F = 3.2, P = 0.07). ICP full time equivalents (FTEs) per 100 beds increased from 0.5 (SD 0.2) in 1999 to 0.8 (SD 0.3) in 2005 (F = 90.8, P < 0.0001). However, the proportion of ICPs in hospitals certified by the Certification Board of Infection Control (CBIC) decreased from 53% (SD 46) in 1999 to 38% (SD 36) in 2005 (F = 8.7, P = 0.004). CONCLUSIONS Canadian infection control programs in 2005 continued to fall short of expert recommendations for human resources and surveillance and control activities. Meanwhile, Nosocomial MRSA rates more than doubled between 1999 and 2005 and hospitals reporting new nosocomial VRE cases increased 77% over the same period. While investments have been made towards infection control programs in Canadian acute hospitals, the rapid rise in ICP positions has not yet translated into marked improvements in surveillance and control activities. In the face of substantial increases in ARO rates in Canada, continued efforts to train ICPs and support hospital infection control programs are necessary.


title: Achievements and challenges in antiviral drug discovery.

text: The last 40 years have seen the development of several antiviral drugs with therapeutic value in treating life-threatening or debilitating diseases such as those caused by HIV, hepatitis B virus, herpesviruses (such as herpes simplex virus and varicella zoster virus) and influenza virus. These relatively recent advances have been due to technical breakthroughs in the cultivation of viruses in the laboratory, identification of viral enzymes and, more recently, their molecular biology. We describe here the antecedence of several of the existing antivirals and their strengths and weaknesses. We indicate where the major challenges lie for future improvements of current therapies and possible new indications, such as hepatitis C virus and papillomavirus. We also describe how current antiviral therapies are restricted to a rather limited number of viral diseases of sufficient interest to the pharmaceutical industry. Finally we describe the potential threat of emerging viruses and bio-weapons and the challenges that they present to therapy.


title: 18F-FDG PET in sarcoidosis: an observational study in 12 patients treated with infliximab.

text: BACKGROUND 18F-FDG PET is a promising technique in sarcoidosis imaging, although it is not incorporated in routine activity assessment. The purpose of this study was to correlate 18F-FDG PET with standard sarcoidosis activity parameters during infliximab treatment. METHODS Twelve patients with refractory sarcoidosis were treated with 6 cycles of infliximab. Pre- and post-therapy 18F-FDG PET was visually evaluated and SUVmax was measured. In addition, the effect of infliximab was evaluated by changes in symptoms, angiotensin converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), vital capacity (VC), diffusion capacity of the lung for carbon monoxide (DLCO) and chest radiography. SUVmax and conventional parameters were correlated. RESULTS Clinical improvement as judged by conventional parameters was seen in all patients, though with a minor response in one. Symptoms improved in 11/12 patients while chest radiographic stages did not change. The decrease in ACE was 39% and in sIL-2R 47% (p<0.01). Improvement of VC and DLCO was 5.4% and 3.3% (p<0.05), respectively. 18F-FDG PET revealed either improvement or normalization in 11/12 (92%) clinically responding patients. The overall decrease in SUVmax was 55% (p<0.01); the patient with a limited response showed a 34% increase. A decrease in SUVmax of the lung parenchyma correlated with an improvement of VC (r=-0.75, p<0.01). No significant correlation between SUVmax and other parameters was found. CONCLUSION Changes imaged by 18F-FDG PET during infliximab treatment in sarcoidosis patients correlate with signs of clinical improvement to a considerate extent, which supports the hypothesis that 18F-FDG uptake represents disease activity.


title: Capnocytophaga sp. isolated from a cat with chronic sinusitis and rhinitis.

text: A Capnocytophaga sp. was inadvertently isolated from a cat with chronic sinusitis and rhinitis when cytopathic effects were observed in Crandall-Reese feline kidney cells that had been inoculated with oropharyngeal swab samples. Although Capnocytophaga spp. are of considerable zoonotic importance, their clinical relevance for dogs or cats has not been established. However, failure to do so may be attributed to the infrequent use of specialized isolation techniques that are required to grow Capnocytophaga spp. To our knowledge, successful isolation of these organisms from a cat with nasopharyngeal disease has not been reported.


title: A pilot study using preoperative cerebral tissue oxygen saturation to stratify cardiovascular risk in major non-cardiac surgery.

text: This prospective pilot study evaluated whether low preoperative cerebral tissue oxygen saturation is associated with unfavourable outcomes after major elective non-cardiac surgery. Eighty-one patients over 60 years of age, American Society of Anesthesiologists physical status 3 or 4, were recruited. Resting cerebral tissue oxygen saturation was recorded on room air, and after oxygen supplementation, using cerebral oximetry. The primary outcome was 30-day major adverse event of combined mortality or severe morbidity, and the secondary outcome was 30-day new disability. Eleven patients (13.6%) suffered a major adverse event, and 28 patients (34.6%) experienced new disability. Room air cerebral tissue oxygen saturation was significantly different between patients who had a major adverse event, 67% (95% confidence interval [CI] 65-70) versus unaffected, 71% (95% CI 70-72; P=0.04). No statistical difference was found between patients for new disability (range 70%-74%; P=0.73). Room air cerebral tissue oxygen saturation was significantly associated with major adverse events (odds ratio 1.36 (95% CI 1.03-1.79), P=0.03). Saturation levels ≤68% carried a positive likelihood ratio of 2.2 for death or severe morbidity, P=0.04. A definitive trial is required to confirm if cerebral oximetry can be used to stratify the cardiovascular risk of patients presenting for non-cardiac surgery.


title: Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus.

text: A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.


title: Antiviral antibodies are necessary to prevent cytotoxic T-lymphocyte escape in mice infected with a coronavirus.

text: Mutation within virus-derived CD8 T-cell epitopes can effectively abrogate cytotoxic T-lymphocyte (CTL) recognition and impede virus clearance in infected hosts. These so-called "CTL escape variant viruses" are commonly selected during persistent infections and are associated with rapid disease progression and increased disease severity. Herein, we tested whether antiviral antibody-mediated suppression of virus replication and subsequent virus clearance were necessary for preventing CTL escape in coronavirus-infected mice. We found that compared to wild-type mice, B-cell-deficient mice did not efficiently clear infectious virus, uniformly developed clinical disease, and harbored CTL escape variant viruses. These data directly demonstrate a critical role for antiviral antibody in protecting from the selective outgrowth of CTL escape variant viruses.


title: Type IVB pilus operon promoter controlling expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid gene in Salmonella enterica Serovar Typhi elicits full immune response by intranasal vaccination.

text: Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.


title: Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells.

text: Coronavirus contains three envelope proteins, M, E and S, and a nucleocapsid, which consists of genomic RNA and N protein, within the viral envelope. We studied the macromolecular interactions involved in coronavirus assembly in cells infected with a murine coronavirus, mouse hepatitis virus (MHV). Coimmunoprecipitation analyses demonstrated an interaction between N protein and M protein in infected cells. Pulse-labeling experiments showed that newly synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi compartment, which is part of the MHV budding site. Coimmunoprecipitation analyses further revealed that M protein interacted with only genomic-length MHV mRNA, mRNA 1, while N protein interacted with all MHV mRNAs. These data indicated that M protein interacted with the nucleocapsid, consisting of N protein and mRNA 1, in infected cells. The M protein-nucleocapsid interaction occurred in the absence of S and E proteins. Intracellular M protein-N protein interaction was maintained after removal of viral RNAs by RNase treatment. However, the M protein-N protein interaction did not occur in cells coexpressing M protein and N protein alone. These data indicated that while the M protein-N protein interaction, which is independent of viral RNA, occurred in the M protein-nucleocapsid complex, some MHV function(s) was necessary for the initiation of M protein-nucleocapsid interaction. The M protein-nucleocapsid interaction, which occurred near or at the MHV budding site, most probably represented the process of specific packaging of the MHV genome into MHV particles.


The risk of a pandemic with the influenza A (H1N1) virus.


title: [The biological characteristics of SARS virus and its related coronaviruses].

text: Cases of the life-threatening respiratory disease with no identified cause (designated as "severe acute respiratory syndrome", SARS, in March 2003) were first reported in late 2002 from Guangdong Province, China; they were followed by reports from about other 30 countries (or regions) such as Vietnam, Singapore, Thailand, Hong Kong (China), Canada, and USA etc. Because of its ongoing epidemic and high death rate, SARS has shined an intense spotlight all over the world. The World Health Organization (WHO) has promptly established a network of international laboratories consisting of 13 members around the 10 countries to facilitate the identification of the causative agent of SARS. A novel coronavirus, SARS virus, fulfilling all of Koch's postulates was announced to be the primary aetiological agent of SARS on April 16 by WHO shortly after the Canadian scientists released the full-length genome sequence of SARS virus (Tor2) on April 12. China is now facing a formidable task to fight SARS. In this article, we present a brief summary on the biological characteristics of coronavirus with its associated diseases, and make some suggestions on how to curb this outbreak and how to cure SARS disease based on the potential targets of this novel virus.


title: Rapid and efficient preparation of monoclonal antibodies against SARS-associated coronavirus nucleocapsid protein by immunizing mice.

text: OBJECTIVE To develop a rapid and efficient method for preparing monoclonal antibodies (mAb) against SARS-associated coronavirus (SARS-Cov) nucleocapsid (N) protein. METHODS BALB/c mice were injected with the recombinant N protein of SARS-Cov into the foot-pads for the immunization, and the popliteal lymph nodes were isolated 15 d later for mAb-producing hybridomas, from which the mAbs against the N protein of SARS-Cov were screened. The identification of the mAb against the N protein of SARS-Cov was performed using indirect enzyme-linked immunosorbent assay (ELISA), indirect fluorescent-antibody assay (IFA), and Western immunoblotting. RESULTS Four strains of hybridomas were obtained that produced the mAb specific to the N protein without detectable cross-reactivity with other pathogens. Of the 4 strains, 2 were identified as the immunoglobulin G1 (IgG1) isotype, 1 IgG2a, and the other IgG2b, with affinity constants (Ka) of 2 of the strains being 4.14 x 10(-9)M and 3.19 x 10(-9)M respectively. CONCLUSION This is the first report on the preparation of mAb that is specific to the SARS-Cov, and the high-specificity and high-affinity mAb produced by the 4 strains of hybridomas provide a basis for further researches on the pathogenesis and early diagnosis of SARS.


title: The severe acute respiratory syndrome coronavirus nucleocapsid protein is phosphorylated and localizes in the cytoplasm by 14-3-3-mediated translocation.

text: The severe acute respiratory syndrome coronavirus(SARS-CoV) nucleocapsid (N) protein is one of the four structural proteins of the virus and is predicted to be a 46-kDa phosphoprotein. Our in silico analysis predicted N to be heavily phosphorylated at multiple residues. Experimentally, we have shown in this report that the N protein of the SARS-CoV gets serine-phosphorylated by multiple kinases, in both the cytoplasm and the nucleus. The phosphoprotein is stable and localizes in the cytoplasm and coprecipitates with the membrane fraction. Also, using specific inhibitors of phosphorylation and an in vitro phosphorylation assay, we show that the nucleocapsid protein is a substrate of cyclin-dependent kinase (CDK), glycogen synthase kinase, mitogen-activated protein kinase, and casein kinase II. Further, we show that the phosphorylated protein is translocated to the cytoplasm by binding to 14-3-3 (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein). 14-3-3 proteins are a family of highly conserved, ubiquitously expressed eukaryotic proteins that function primarily as adapters that modulate interactions between components of various cellular signaling and cell cycle regulatory pathways through phosphorylation-dependent protein-protein interactions. Coincidentally, the N protein was also found to downregulate the expression of the theta isoform of 14-3-3 (14-3-3theta), leading to the accumulation of phosphorylated N protein in the nucleus, in the absence of growth factors. Using short interfering RNA specific to 14-3-3theta we have inhibited its expression to show accumulation of phosphorylated N protein in the nucleus. Thus, the data presented here provide a possible mechanism for phosphorylation-dependent nucleocytoplasmic shuttling of the N protein. This 14-3-3-mediated transport of the phosphorylated N protein and its possible implications in interfering with the cellular machinery are discussed.


title: Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells.

text: In order to establish nonlytic persistent infections (PI) of BHK cells, replicons derived from Sindbis (SIN) and Semliki Forest (SFV) viruses have mutations in nsP2. Five different nsP2 PI replicons were compared to wild-type (wt) SIN, SFV, and wt nsPs SIN replicons. Replicon PI BHK21 cells had viral RNA synthesis rates that were less than 5% of those of the wt virus and approximately 10% or less of those of SIN wt replicon-infected cells, and, in contrast to wt virus and replicons containing wt nsP2, all showed a phenotype of continuous minus-strand synthesis and of unstable, mature replication/transcription complexes (RC+) that are active in plus-strand synthesis. Minus-strand synthesis and incorporation of [3H]uridine into replicative intermediates differed among PI replicons, depending on the location of the mutation in nsP2. Minus-strand synthesis by PI cells appeared normal; it was dependent on continuous P123 and P1234 polyprotein synthesis and ceased when protein synthesis was inhibited. The failure by the PI replicons to shut off minus-strand synthesis was not due to some defect in the PI cells but rather was due to the loss of some function in the mutated nsP2. This was demonstrated by showing that superinfection of PI cells with wt SFV triggered the shutdown of minus-strand synthesis, which we believe is a host response to infection with alphaviruses. Together, the results indicate alphavirus nsP2 functions to engage the host response to infection and activate a switch from the early-to-late phase. The loss of this function leads to continuous viral minus-strand synthesis and the production of unstable RC+.


title: Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of pseudotyped virus.

text: The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the putative envelope glycoproteins, when expressed as recombinant proteins in mammalian cells, largely accumulate in the endoplasmic reticulum. In this study, genomic regions which include the putative ectodomain of the E1 (amino acids 174 to 359) and E2 (amino acids 371 to 742) glycoproteins were appended to the transmembrane domain and cytoplasmic tail of vesicular stomatitis virus (VSV) G protein. This provided a membrane anchor signal and the VSV incorporation signal at the carboxy termini of the E1 and E2 glycoproteins. The chimeric gene constructs exhibited expression of the recombinant proteins on the cell surface in a transient expression assay. When infected with a temperature-sensitive VSV mutant (ts045) and grown at the nonpermissive temperature (40.5 degrees C), cells transiently expressing the E1 or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The resulting pseudotyped virus generated from E1 or E2 surprisingly exhibited the ability to infect mammalian cells and sera derived from chimpanzees immunized with the homologous HCV envelope glycoproteins neutralized pseudotyped virus infectivity. Results from this study suggested a potential functional role for both the E1 and E2 glycoproteins in the infectivity of VSV/HCV pseudotyped virus in mammalian cells. These observations further suggest the importance of using both viral glycoproteins in a candidate subunit vaccine and the potential for using a VSV/HCV pseudotyped virus to determine HCV neutralizing antibodies.


title: Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.

text: To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen approximately 400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.


As the bat flies.


title: Current vaccine adjuvants: an overview of a diverse class.

text: Numerous compounds are under evaluation as immunological adjuvants for improvement of vaccine performance. This review will briefly summarize some of the many diverse substances that are currently being utilized as vaccine adjuvants in preclinical and clinical studies.


title: Soft-tissue Defects After Total Knee Arthroplasty: Management and Reconstruction.

text: Wound healing complications associated with total knee arthroplasty present a considerable challenge to the orthopaedic surgeon. To ensure preservation of a functional joint, the management of periprosthetic soft-tissue defects around the knee requires rapid assessment, early and aggressive débridement, and durable, contoured coverage. Several reconstructive options are available to tailor soft-tissue coverage to the location, size, and depth of the wound. Special consideration should be given to the timing of the intervention, management of infection, and prosthesis salvage. The merits of each reconstructive option, including perforator, fasciocutaneous, muscular, and free microvascular flaps, should be weighed to select the most appropriate option. The proposed approach can guide surgeons in treating patients with these complex soft-tissue defects.


docid: jtslhbib

title: Talk to Patients About: Why Will It Take So Long for a COVID-19 Vaccine?

text: Of all the solutions to the COVID-19 pandemic, a vaccine is the most attractive. With just one shot, people could transform the disease from a global disruptor to an easily manageable public health problem. But vaccines can't be whipped up overnight.


title: Thrombus in Transit and Impending Pulmonary Embolism Detected on POCUS in a Patient with COVID-19 Pneumonia.

text: Coronavirus disease 2019 (COVID-19) is a pandemic that started in China in December 2019 and carries a high risk of morbidity and mortality. To-date (4-22-2020) it affected over 2.6 million people and resulted in nearly 200,000 death worldwide mainly due to severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Among the major underlying pathophysiologic mechanisms in COVID 19 is hypercoagulability, leading to increased risk for deep vein thrombosis and pulmonary embolism that contribute to increased morbidity and mortality. In this report, we present the case of a 55-year-old man who presented with COVID-19 pneumonia, and was found to have a thrombus in transit by routine point of care ultrasound (POCUS). While computer tomography (CT) angiography is the test of choice, the utilization of point of care ultrasound (POCUS) has gained traction as an adjunctive means of surveillance for the development of VTE in patients with COVID-19. In this report, we discuss the clinical utility of POCUS in diagnosing thrombus in transit in COVID 19 populations.


title: Comparison of effectiveness of whole viral, N and N199 proteins by ELISA for the rapid diagnosis of severe acute respiratory syndrome coronavirus.

text: BACKGROUND Although severe acute respiratory syndrome (SARS) has been controlled, the subsequently emerging sporadic cases in 2004 emphasize the necessity of developing a rapid diagnostic method, which would be of great help in clinical diagnosis and also wild host screening. This study aims to establish an effective and rapid serological tool for the diagnosis of SARS-CoV by comparison among whole viral, N and N199 proteins by ELISA. METHODS SARS-CoV N and N199 (a truncated nucleocapsid gene) genes were cloned, expressed, identified by Western blotting, and applied in screening of human and swine samples. Sera of SARS convalescent-phase patients, normal human sera, sera of patients with other respiratory diseases, and swine sera were screened by ELISA, with whole SARS-CoV F69, N and N199 proteins as antigens. RESULTS The sensitivity and specificity of N and N199 proteins in human sera diagnosis were approximate (P = 0.743), which was higher than whole viral protein but the difference was not significant (P = 0.234). The N199 protein proved to be more specific in swine sera screening than whole viral and N protein (P < 0.001). CONCLUSION N199 protein is feasible in both clinical diagnosis and SARS-CoV reservoir screening.


title: SARS commission reports on the Canadian outbreak.

text: The third and final report investigating the 2003 Toronto outbreak of severe acute respiratory syndrome (SARS) that led to 44 deaths says hospital downsizing was a factor and warns that 'serious problems persist and much needs to be done'.


title: Immunohistochemical identification of porcine respiratory coronavirus antigen in the lung of conventional pigs.

text: Nine 3-week-old conventional pigs were inoculated intranasally with a Korean isolate of porcine respiratory coronavirus (PRCV). Three 3-week-old conventional pigs were kept as noninoculated controls. Three inoculated and one control pig were euthanatized at 5, 10, and 15 days postinoculation (DPI), respectively. All nine inoculated pigs developed respiratory disease. Interstitial pneumonia characterized by mononuclear inflammatory cell infiltration into alveolar septa were seen microscopically in all nine PRCV-infected pigs. Histopathologic changes were severe at DPI, modest at 10 DPI, and almost resolved at 15 DPI. PRCV antigen was not detected in bronchial and bronchiolar epithelium but was detected in interstitial macrophages in the lungs. This Korean isolate of PRCV appeared to replicate primarily within alveolar macrophages in the respiratory system of the pig.


title: O-glycosylation of the coronavirus M protein. Differential localization of sialyltransferases in N- and O-linked glycosylation.

text: It has previously been shown that the M (E1) glycoprotein of mouse hepatitis virus strain A59 (MHV-A59) contains only O-linked oligosaccharides and localizes to the Golgi region when expressed independently. A detailed pulse-chase analysis was made of the addition of O-linked sugars to the M protein; upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, three different electrophoretic forms could be distinguished that corresponded to the sequential acquisition of N-acetylgalactosamine (GalNAc), galactose (Gal), and sialic acid (SA). A fourth and fifth form could also be detected which we were unable to identify. Following Brefeldin A treatment, the M protein still acquired GalNAc, Gal, and SA, but the fourth and fifth forms were absent, suggesting that these modifications occur in the trans-Golgi network (TGN). In contrast, in the presence of BFA, the G protein of vesicular stomatitis virus (VSV), which contains N-linked oligosaccharides, acquired Gal and fucose but not SA. These results are consistent with earlier published data showing that Golgi compartments proximal to the TGN, but not the TGN itself, relocate to the endoplasmatic reticulum/intermediate compartment. More importantly, our data argue that, whereas addition of SA to N-linked sugars occurs in the TGN the acquisition of both SA on O-linked sugars and the addition of fucose to N-linked oligosaccharides must occur in Golgi compartments proximal to the TGN. The glycosylation of the M protein moreover indicates that it is transported to trans-Golgi and TGN. This was confirmed by electron microscopy immunocytochemistry, showing that the protein is targeted to cisternae on the trans side of the Golgi and co-localizes, at least in part, with TGN 38, a marker of the TGN, as well as with a lectin specific for sialic acid.


title: Aetiology of acute gastroenteritis in infancy and early childhood in southern India.

text: The aetiology of acute gastroenteritis was studied in 50 infants and young children. Bacterial pathogens were isolated in 33, enteropathogenic E. coli (EPEC), Salmonella, and Shigella being the commonest isolates. Rotaviruses were detected in the stools of 13 of the cases. All children with gastroenteritis in whom rotavirus was detected were seen during the months July to December. In 30 children who served as controls, EPEC were isolated in 6, but rotavirus was detected in none. It is concluded that infection with rotaviruses is a significant cause of morbidity in children with gastroenteritis in southern India.


title: Neonatal calf diarrhea caused by a virus that induces villous epithelial cell syncytia.

text: Intestinal lesions caused by a virus serologically unrelated to the calf diarrheal rotavirus or coronavirus were studied in gnotobiotic calves. The virion purified from feces from infected calves was a fringed particle with a diameter of about 100 nm. The incubation period from time of inoculation per orum to onset of diarrhea in calves was as short as 8 hours. The viral infection in bacteria-free calves or calves not contaminated with pathogenic bacteria caused severe illness for only 24 hours. When bacteria such as the K99 antigen Escherichia coli were present, the combined infection caused mortality. Lesions occurred only in the small intestinal villous epithelium. Calves euthanatized shortly before or after the onset of diarrhea had developed villous epithelial cell syncytia that contained numberous virions in the cytoplasm. Within 2 to 3 hours after onset of diarrhea, the infected cells were shed and the villi had denuded tips or had cuboidal to squamous epithelial cells.


title: Subunit composition and conformational stability of the oligomeric form of the avian reovirus cell-attachment protein sigmaC.

text: Previous work has shown that the avian reovirus cell-attachment sigma C (sigmaC) protein is a multimer. In the first part of this study the oligomerization state of intracellularly synthesized sigmaC was analysed by different approaches, including SDS-PAGE, chemical cross-linking, sedimentation and gel filtration analysis. All these approaches indicated that protein sigmaC in its native state is a homotrimer. In the second part of the present work we investigated the effect of different factors and reagents on oligomer stability, in order to elucidate the nature of the forces that maintain the conformational stability of the homotrimer. Our results, based on the stabilizing effect conferred by reducing agents, demonstrate that the sigmaC subunits are not covalently bound via disulfide linkages. They further suggest that the formation of an intrachain disulfide bond between the two cysteine residues of the sigmaC polypeptide has a negative effect on oligomer stability. The susceptibility of the trimer to pH, temperature, ionic strength, chemical denaturants and detergents indicates that hydrophobic interactions contribute much more to oligomer stability than do ionic interactions and hydrogen bonding. Finally, our results also reveal that mammalian and avian reovirus cell attachment proteins follow different subunit dissociation pathways.


title: A 9,000-year record of Chagas' disease.

text: Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from approximately 9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, approximately 450 B.P. ( approximately 1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite.


The 1918-1919 Influenza Pandemic and National Amnesia.


docid: rtdijwum

title: Cellular receptors for transmissible gastroenteritis virus on porcine enterocytes.

text: The activity of aminopeptidase-N (APN), reported to be a major receptor for porcine transmissible gastroenteritis virus (TGEV), in enterocyte fractions harvested from the jejunal villi and crypts of newborn and weaned piglets, did not correspond with the levels of saturable virus binding previously demonstrated for the same fractions. Plasma membranes prepared from enterocytes harvested from the jejunal villi of a newborn piglet were used in the preparation of a monoclonal antibody (MAb) which blocked the binding of TGEV, but not that of the porcine respiratory coronavirus (PRCV), to ST cells. This MAb immunoprecipitated a 200 kDa non-glycosylated protein from lysates of ST cells, which was not precipitated by an anti-APN MAb. The 200 kDa protein was shown by immunostaining and fluorescence activated cell scanning to be present on ST cells and on villous enterocytes from newborn piglets, but not on MDBK cells or enterocytes from weaned piglets. APN was demonstrated by the same techniques to be present on villous enterocytes from both newborn and weaned piglets, as well as on ST cells. It was concluded that the 200 kDa protein may be a second receptor for TGEV, contributing to the high susceptibility of newborn piglets to the virus.


title: Coronavirus E1 glycoprotein expressed from cloned cDNA localizes in the Golgi region.

text: Cloned cDNA encoding the membrane glycoprotein E1 of the coronavirus mouse hepatitis virus strain A59 was expressed transiently in a monkey fibroblast cell line (COS) by using a simian virus 40-based vector. As determined by indirect immunofluorescence microscopy, the E1 protein accumulated intracellularly in a perinuclear region coincident with a Golgi marker. The same three species of E1 that occur in virus-infected cells were also found in transfected cells. These are one unglycosylated form and two apparently O-glycosylated forms that could be labeled in a tunicamycin-resistant fashion with [3H]glucosamine. Because O glycosylation occurs posttranslationally in the Golgi apparatus, we could show, by monitoring the rate of acquisition of oligosaccharides, that the transport of E1 from the rough endoplasmic reticulum to the Golgi apparatus had a half time of between 15 and 30 min.


title: Outbreak of norovirus illness in a college summer camp: impact of cleaning on occurrence of norovirus on fomites.

text: During the summer of 2005 an outbreak of norovirus acute gastroenteritis occurred in a residential college summer camp and was reported to the local health department. The outbreak spread rapidly to several other groups concurrently sharing the same facilities. During the investigation, fomites were sampled at different times in dorm rooms and tested for norovirus. The number of norovirus-positive rooms increased after the first room cleaning, from 40% to 73%. After the initial cleaning, the staff was instructed on proper cleaning and disinfection procedures and provided with disposable disinfecting wipes to reduce cross contamination, and the number of norovirus-positive rooms decreased to 30%. These findings reinforce the need for appropriate cleaning and disinfection procedures during a norovirus outbreak.


title: Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis.

text: AIM To obtain the pure sample of SARS small envelope E protein (SARS E protein), study its properties and analyze its possible functions. METHODS The plasmid of SARS E protein was constructed by the polymerase chain reaction (PCR), and the protein was expressed in the E coli strain. The secondary structure feature of the protein was determined by circular dichroism (CD) technique. The possible functions of this protein were annotated by bioinformatics methods, and its possible three-dimensional model was constructed by molecular modeling. RESULTS The pure sample of SARS E protein was obtained. The secondary structure feature derived from CD determination is similar to that from the secondary structure prediction. Bioinformatics analysis indicated that the key residues of SARS E protein were much conserved compared to the E proteins of other coronaviruses. In particular, the primary amino acid sequence of SARS E protein is much more similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses. The transmembrane (TM) segment of the SARS E protein is relatively more conserved in the whole protein than other regions. CONCLUSION The success of expressing the SARS E protein is a good starting point for investigating the structure and functions of this protein and SARS coronavirus itself as well. The SARS E protein may fold in water solution in a similar way as it in membrane-water mixed environment. It is possible that beta-sheet I of the SARS E protein interacts with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a random structure in water solution.


title: Immunization against feline coronaviruses.

text: Feline infectious peritonitis (FIP) is caused by one of several strains of feline coronaviruses which are grouped into 2 general types of viruses. Infection of cats with FIP virus results in production of serum antibodies which may be protective in conjunction with cell mediated immunity, may provided no protection at all, or may produce an immune enhancement to subsequent exposure to another FIP virus or a recrudescence of the original infecting virus. Attempts at immunization of cats against FIP with inactivated or live FIP viruses have been generally unsuccessful, and often sensitizing the cat through immune enhancement rather than providing protection. Heterologous live virus vaccines using viruses of the same antigenic cluster (transmissible gastroenteritis of swine, canine coronavirus, and human coronavirus 229E) have failed to provide protection against FIP virus. Further research into the exact mechanism of protection and immune enhancement is needed in order to understand ways of producing an effective and safe vaccine.


title: Evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in Beijing, 2003.

text: CONTEXT Beijing, China, experienced the world's largest outbreak of severe acute respiratory syndrome (SARS) beginning in March 2003, with the outbreak resolving rapidly, within 6 weeks of its peak in late April. Little is known about the control measures implemented during this outbreak. OBJECTIVE To describe and evaluate the measures undertaken to control the SARS outbreak. DESIGN, SETTING, AND PARTICIPANTS Data were reviewed from standardized surveillance forms from SARS cases (2521 probable cases) and their close contacts observed in Beijing between March 5, 2003, and May 29, 2003. Procedures implemented by health authorities were investigated through review of official documents and discussions with public health officials. MAIN OUTCOME MEASURES Timeline of major control measures; number of cases and quarantined close contacts and attack rates, with changes in infection control measures, management, and triage of suspected cases; and time lag between illness onset and hospitalization with information dissemination. RESULTS Health care worker training in use of personal protective equipment and management of patients with SARS and establishing fever clinics and designated SARS wards in hospitals predated the steepest decline in cases. During the outbreak, 30 178 persons were quarantined. Among 2195 quarantined close contacts in 5 districts, the attack rate was 6.3% (95% confidence interval [CI], 5.3%-7.3%), with a range of 15.4% (95% CI, 11.5%-19.2%) among spouses to 0.36% (95% CI, 0%-0.77%) among work and school contacts. The attack rate among quarantined household members increased with age from 5.0% (95% CI, 0%-10.5%) in children younger than 10 years to 27.6% (95% CI, 18.2%-37.0%) in adults aged 60 to 69 years. Among almost 14 million people screened for fever at the airport, train stations, and roadside checkpoints, only 12 were found to have probable SARS. The national and municipal governments held 13 press conferences about SARS. The time lag between illness onset and hospitalization decreased from a median of 5 to 6 days on or before April 20, 2003, the day the outbreak was announced to the public, to 2 days after April 20 (P<.001). CONCLUSIONS The rapid resolution of the SARS outbreak was multifactorial, involving improvements in management and triage in hospitals and communities of patients with suspected SARS and the dissemination of information to health care workers and the public.


title: Identification of a domain required for autoproteolytic cleavage of murine coronavirus gene A polyprotein.

text: The 5'-most gene of the murine coronavirus genome, gene A, is presumed to encode viral RNA-dependent RNA polymerase. It has previously been shown that the N-terminal portion of this gene product is cleaved into a protein of 28 kilodaltons (p28). To further understand the mechanism of synthesis of the p28 protein, cDNA clones representing the 5'-most 5.3 kilobases of murine coronavirus mouse hepatitis virus strain JHM were sequenced and subcloned into pT7 vectors from which RNAs were transcribed and translated in vitro. The sequence was found to encode a single long open reading frame continuing from near the 5' terminus of the genome. Although p28 is encoded from the first 1 kilobase at the 5' end of the genome, translation of in vitro-transcribed RNAs indicated that this protein was not detected unless the product of the entire 5.3-kilobase region was synthesized. Translation of RNAs of 3.9 kilobases or smaller yielded proteins which contained the p28 sequence, but p28 was not cleaved. This suggests that the sequence in the region between 3.9 and 5.3 kilobases from the 5' end of the genomic RNA is essential for proteolytic cleavage and contains autoproteolytic activity. The p28 protein could not be cleaved from the smaller primary translation products of gene A, even in the presence of the larger autocleaving protein. Cleavage of the p28 protein was inhibited by addition of the protease inhibitor ZnCl2. This study thus identified a protein domain essential for autoproteolytic cleavage of the gene A polyprotein.


title: Type and quantity of data needed for an early estimate of transmissibility when an infectious disease emerges.

text: An early estimate of disease transmissibility is essential for a well-informed public health response to a newly emerged infectious disease. In this study, we ask what type and quantity of data are needed for useful estimation of the initial reproduction number (R). It is possible to estimate R from case incidence data alone when the growing incidence of cases displays a wave pattern, because the pattern provides information about the serial interval (the time elapsed between the onset of symptoms of a case and symptom onset in individuals infected by that case). When the mode of the serial interval distribution is small, 1.5 days or less, there is generally no informative wave pattern in the observed series of daily incidences. The precision of the estimate of R is then improved substantially by having some observations on the serial interval. For an infectious disease with characteristics such as those of influenza, an estimate of R able to inform plans to mitigate transmission is obtained when the cumulative incidence of cases reaches about 300 and about 10 observations on the serial interval are available.


title: Multistate outbreak of human Salmonella typhimurium infections associated with aquatic frogs - United States, 2009.

text: During April-July 2009, the Utah Department of Health identified five cases of Salmonella Typhimurium infection with indistinguishable pulsed-field gel electrophoresis (PFGE) patterns, predominantly among children. In August, CDC began a multistate outbreak investigation to determine the source of the infections. This report summarizes the results of this ongoing investigation, which, as of December 30, had identified 85 S. Typhimurium human isolates with the outbreak strain from 31 states. In a multistate case-control study, exposure to frogs was found to be significantly associated with illness (63% of cases versus 3% of controls; matched odds ratio [mOR] = 24.4). Among 14 case-patients who knew the type of frog, all had exposure to an exclusively aquatic frog species, the African dwarf frog. Environmental samples from aquariums containing aquatic frogs in four homes of case-patients yielded S. Typhimurium isolates matching the outbreak strain. Preliminary traceback information has indicated these frogs likely came from the same breeder in California. Reptiles (e.g., turtles) and amphibians (e.g., frogs) have long been recognized as Salmonella carriers, and three multistate outbreaks of human Salmonella infections associated with turtle contact have occurred since 2006. However, this is the first reported multistate outbreak of Salmonella infections associated with amphibians. Educational materials aimed at preventing salmonellosis from contact with reptiles should be expanded to include amphibians, such as aquatic frogs.


title: Structural proteins of equine arteritis virus.

text: We have recently shown that the genome of equine arteritis virus (EAV) contains seven open reading frames (ORFs). We now present data on the structural proteins of EAV and the assignment of their respective genes. Virions are composed of a 14-kDa nucleocapsid protein (N) and three membrane proteins designated M, GS, and GL. M is an unglycosylated protein of 16 kDa, and GS and GL are N-glycosylated proteins of 25 and 30 to 42 kDa, respectively. The broad size distribution of GL results from heterogeneous N-acetyllactosamine addition since it is susceptible to digestion by endo-beta-galactosidase. Using monospecific antisera as well as an antivirion serum, and by expression of individual ORFs, the genes for the structural proteins were identified: ORF 7 codes for N, ORF 6 for M, ORF 5 for GL, and ORF 2 for GS. With the exception of GS, the proteins are about equally abundant in EAV virions, being present at a molar ratio of 3 (N):2 (M):3 (GL). The GS protein, which is expressed at a level similar to that of M in infected cells, is strikingly underrepresented in virus particles (1 to 2%). Our data justify a distinct taxonomic position for EAV, together with lactate dehydrogenase-elevating virus and simian hemorrhagic fever virus; although coronavirus- and toroviruslike in features of transcription and translation, the virion architecture of EAV is fundamentally different.


title: Enterotoxigenic Escherichia coli (ETEC) in farm animals.

text: Animal diseases due to enterotoxigenic Escherichia coli (ETEC) typically appear as severe watery diarrhoea during the first few days of life (also a few days after weaning in pigs). ETEC adhere to the small intestinal microvilli without inducing morphological lesions and produce enterotoxins acting locally on enterocytes. This action results in the hypersecretion (of water and electrolytes) and reduced absorption. Adhesins and toxins are the two prominent virulence attributes of ETEC and the level of knowledge of these factors determines the chances for successful prevention and therapy of the disease. For animal ETEC the most common adhesins are the fimbriae (pili) on the surface: F4(K88), F5(K99), F6(987P), F41, F42, F165, F17 and F18. Enterotoxins (extracellular proteins or peptides) of animal ETEC are classified as heat-labile (LT) and heat-stable (ST) enterotoxins with further subdivisions (LTh-I, LTp-I, LTIIa, LTIIb, STaH, STaP, STb) according to antigenic and biological differences. Fimbriae and LT enterotoxins are made up of large molecular weight proteins which facilitate their utilisation in vaccines and their detection using immunodiagnostic systems. The adhesive fimbriae and enterotoxins of animal ETEC are plasmid determined (except F41 and F17). Virulence gene probes (DNA hybridisation, PCR) are specific and sensitive diagnostic and epidemiologic tools for the detection of ETEC. Based on genetic typing, the ETEC, in spite of limited serogroups, seem to represent a population of E. coli with a diverse genetic background.


title: [Use of multiplex PCR method with real-time detection for differential diagnosis of respiratory viral infections].

text: Multiplex real-time polymerase chain reaction test-system with fluorescent detection (RT-PCR) for simultaneous identification of main agents of acute respiratory viral infections: influenza A (IAV) and B viruses (IBV), parainfluenza viruses types 1, 2, 3, 4 (PIV 1 - 4), adenoviruses (ADV), respiratory syncitial virus (RSV), rhinoviruses (RV) and enteroviruses (EV), in presence internal positive control (IPC) represented by vaccine strain of rubella virus RA 27/3. Using multiplex RT-PCR method, respiratory viruses were detected in 116 out of 226 clinical samples (nasal swabs) obtained from patients with symptoms of acute respiratory infection: in 68 (58.6%) samples--IBV; in 21 (18.1%)--IAV; in 12 (10.3%) --RV; in 6 (5.2%)--PIV 2; in 4--(3.4%) ADV; in 3 (2.6%)--RSV; in 2 (1.7%)--EV; in 2 (1.7%)--PIV 4; in 1 (0.9%)--PIV 3; in 1 (0.9%)--PIV 1. Mixed infection was observed in 4 (3.4%) patients. PCR assay allowed to reveal various respiratory viruses in 51.3% of samples. At the same time samples were tested for the presence of 12 respiratory viruses--IAV, IBV, PIV 1 - 4, RSV, RV, metapneumoviruses, and coronaviruses NL63, 229E and OC43--in the presence of IPC represented by equine arteritis virus using analogous PCR test-system provided by medical center of Leiden university. Results of tests for detection of IAV, IBV, RSV, PIV 1 - 4, and RV, analyzed by both systems, agreed in 94%. Multiplex format of RT-PCR performing significantly reduces time and cost of the test, which make it suitable and effective instrument of epidemiological studies.


title: Immunogenetics of severe respiratory infections: models for the development of new therapeutic strategies.

text: Innate and adaptive immunity plays a critical role in the defence of the lung and other mucosal surfaces exposed to micro-organisms. Anti-microbial peptides and proteins, cytokines and chemokines are important immune weapons as they build up the protective front for the respiratory tract. The notion that susceptibility to infectious diseases may be inherited is widely accepted and, as it is the failure to activate adaptive immunity that may allow infection to become established and progress toward invasion and dissemination, the recognition of specific gene defects affecting the ability of the immune system to overcome invading pathogens may shed light upon those mechanisms of immune regulation that are playing the most critical roles. The aim of the present review is to discuss some of the advances in infection immunogenetics that may lead to identify new strategies in the development of new anti-infectious and anti-inflammatory drugs.


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title: [Isolation and identification of SARS virus in Guangdong province].

text: BACKGROUND To isolate and identify pathogen of atypical pneumonia in Guangdong. METHODS Pathogens were isolated from variety of samples collected from atypical pneumonia patient by using MDCK cells, and identified with serological and molecular methods. RESULTS A novel coronavirus was isolated from patients with atypical pneumonia, from which an RNA fragment of 279 nt was amplified by nested RT-PCR. And sequence assay showed that only 39-65 percent of sequence of the virus was homogenous to known coronavirus, but almost 100% homogenous (with one base exception, 12a to t) to SARS-associated coronavirus isolated from patients outside Guangdong, such as in Beijing, Hong Kong, Taiwan, Germany, Italy and so on. Indirect immunofluorescence test showed a specific antigen-antibody reactivity between the coronavirus and convalescent-phase sera of SARS patients. CONCLUSION The pathogen of the atypical pneumonia in Guangdong province was a novel type of coronavirus, which could be isolated by using MDCK cells.


title: Necrotizing enterocolitis in full-term newborns.

text: During a 17-month period, 19 full-term newborn infants were hospitalized for necrotizing enterocolitis (NEC). 10 of these infants had no apparent risk factors. Only 7 suffered acute fetal distress. 16 of the 19 infants were born in the same hospital. Toxicological and bacteriological investigations of possible cause revealed no specific agent. Virological analysis of 8 stool samples revealed the presence of corona virus in 5 of the 8.


Ailing Russian health-care system in urgent need of reform.


title: [Study on the myocardiac injury in patients with severe acute respiratory syndrome].

text: OBJECTIVE To explore the myocardiac injury in patients with severe acute respiratory syndrome (SARS) and its clinical significance. METHODS 37 SARS patients fulfilled the Guangdong provincial diagnostic criteria for infectious atypical pneumonia and 35 health controls were investigated. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), troponin I (TnI), creatine kinase-MB (CK-MB) and myoglobin (MYO) were measured. RESULTS CK, LDH and AST levels in patients were higher than those of control group (P < 0.01); furthermore, among patients the levels were higher in fatal cases than in survivors. The positive rates of TnI, CK-MB and MYO in patients were higher than those in controls (P < 0.05). CONCLUSION The patients with SARS are subject to complicating myocardiac injury. Therefore, careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with SARS.


title: Expressing short hairpin RNAs in vivo.

text: Promoter-based expression of short hairpin RNAs (shRNAs) may in principle provide stable silencing of genes in any tissue. As for all approaches that require transgene expression, safe delivery is the biggest obstacle, but toxicity can also occur via expression of the sequence itself. Innate immunity mechanisms can be triggered by expressed hairpin RNAs, critical cellular factors can be saturated, and genes other than the intended target can be silenced. Nevertheless, shRNAs constitute a valuable tool for in vivo research and have great therapeutic potential if the challenges with delivery and side effects are appropriately addressed.


title: Primary care reform in the Peoples' Republic of China: implications for training family physicians for the world's largest country.

text: Just as China has struggled with bringing an expanding economy to a country with large areas of economic underdevelopment, the Chinese health care system is experiencing tension between tradition and modernization. Because of this tension, health care in the Peoples' Republic of China has been undergoing significant reform since the beginning of the 1980s. Experiments in market-based health systems have been unsuccessful and have exacerbated disparities. New reforms, announced in 2006, stress the role of family physicians in leading the health care system. This paper discusses the history of the developments that led up to the new reforms and the educational challenges of training sufficient numbers of family physicians to meet the requirements of the new system.


title: [Molecular detection assays for 2012 identified novel human coronavirus (HCoV) and probe modification with locked nucleic acid (LNA)].

text: OBJECTIVE To develop and optimize the molecular detection assays for recently identified human coronavirus (HCoV) infection. METHODS Based on the 208 base pair(bp) sequence of novel HCoV reported by HPA of UK, we designed and obtained several pairs of primer (F-1, R-1; F-2, R-2) and Taqman probes (TZ1,TZ2) for detection of novel HCoV. Two of probes were modified with LNA (LNA-TZ1, LNA-TZ2). Then, RT-PCR and various real time RT-PCR assays were developed and optimized in this study. We also compared our assays with the real time RT-PCR assays reported recently by Europe team based on upE or ORF1b target. RESULTS The RT-PCR or real time RT-PCR assays for novel HCoV were developed without cross-reactivity with other HCoV and several common respiratory viruses using clinical specimen panel. The analytical sensitivity of assays were less than 50-500 copies per reaction and the detection was improved when Taqman probe modified with LNA-tagged, compared to no LNA-tagged in real time RT-PCR assays. The upE and LNA-TZ1 based assays were better than others. CONCLUSION The molecular detection sensitivity and specificity of TaqMan-based real time PCR assay could be improved when probe tagged with LNA. The upE or LNA-TZ1 based real time RT-PCR assay was recommend for detection of novel HCoV. This study laid a foundation for improving the performance of novel HCoV detection.


Investigation of bovine viral diarrhoea virus-associated abortion in cattle vaccinated with inactivated vaccine.


Reasons for abortion.


title: Intracellular targeting signals contribute to localization of coronavirus spike proteins near the virus assembly site.

text: Coronavirus budding at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) requires accumulation of the viral envelope proteins at this point in the secretory pathway. Here we demonstrate that the spike (S) protein from the group 3 coronavirus infectious bronchitis virus (IBV) contains a canonical dilysine endoplasmic reticulum retrieval signal (-KKXX-COOH) in its cytoplasmic tail. This signal can retain a chimeric reporter protein in the ERGIC and when mutated allows transport of the full-length S protein as well as the chimera to the plasma membrane. Interestingly, the IBV S protein also contains a tyrosine-based endocytosis signal in its cytoplasmic tail, suggesting that any S protein that escapes the ERGIC will be rapidly endocytosed when it reaches the plasma membrane. We also identified a novel dibasic motif (-KXHXX-COOH) in the cytoplasmic tails of S proteins from group 1 coronaviruses and from the newly identified coronavirus implicated in severe acute respiratory syndrome. This dibasic motif also retained a reporter protein in the ERGIC, similar to the dilysine motif in IBV S. The cytoplasmic tails of S proteins from group 2 coronaviruses lack an intracellular localization signal. The inherent differences in S-protein trafficking could point to interesting variations in pathogenesis of coronaviruses, since increased levels of surface S protein could promote syncytium formation and direct cell-to-cell spread of the infection.


title: Flexor tendon repair with barbed suture: an experimental study.

text: Various suture materials have been used for tendon repair. Barbed suture in particular has been demonstrated to be effective for both wound closure and tendon repair. Ten fresh-frozen flexor digitorum profundus tendons of pig were transected and repaired using the two-strand modified Kirchmayr-Kessler technique. The samples were divided into two groups: 4-0 barbed absorbable polyglyconate sutures and 4-0 monofilament absorbable polyglyconate sutures. We measured tensile strength and distance that the testing system pulled the tendon using a universal testing machine. Tensile strength at which 1 and 2 mm of gapping occurred was measured visually at the repair site. Tendons repaired by barbed sutures showed greater tensile strength than monofilament sutures forming still 2-mm gap. However, statistical significance was obtained only at 1-mm gap formation. We concluded that for tendon repair, barbed sutures were superior material to monofilament sutures because of their greater tensile strength, reducing both the initial tendon load and the risk of dehiscence.


1778: PNEUMOCYSTIS PNEUMONIA REMAINS A DIAGNOSTIC CHALLENGE WITH PCR IN ACUTE SETTINGS.


title: 18th International Conference on Antiviral Research.

text: The 18th International Conference on Antiviral Research (ICAR) was held at the Princess Sofia Hotel in Barcelona, Spain, from 11th-14th April, 2005. This is a yearly international meeting sponsored by the International Society for Antiviral Research (ISAR). The current president of ISAR is John A Secrest 3rd of the Southern Research Institute. The scientific programme committee was chaired by John C Drach from the University of Michigan. ISAR was founded in 1987 to exchange prepublication basic, applied and clinical information on the development of antiviral, chemical and biological agents as well as to promote collaborative research. The ISAR has had a major role in the significant advances of the past decade in the reduction of the societal burdens of viral diseases by the focus of ICAR on the discovery and clinical application of antiviral agents. The 18th ICAR was organised as a series of focus presentations on specific viral groups consisting of oral and poster presentations of original research findings. In addition, the conference included plenary speakers, award presentations, a minisymposium on bioterrorism, and a satellite symposium on clinical antiviral drug developments. The size of the conference (> 50 oral and 250 poster presentations) necessitates limitation to the most noteworthy in the judgment of this reviewer. The current membership of the ISAR is approximately 700 with approximately 50% the membership in attendance.