title: [Acute infectious gastroenteritis in Rio Cuarto: clinic, diagnosis and epidemiology with special reference to viral infections].

text: The objectives of the present study are to describe the clinics view of acute infectious gastroenteritis (GE) at the community, in primary and secondary attention health centers, with special references to viral aetiology (VIGE); to correlate with drinkable water and excrete treatment; to develop for the first time a fast diagnostic using electron microscopy in Río Cuarto, Córdoba, Argentina, considering the university and community collaboration in the viral diagnostic. It has been during one year, 122 cases of acute GE, over its clinics epidemiology and diagnostic aspects (1999-2000). With conventional laboratory methods, it has been determined the bacteria and micotic aetiology (NOVIGE); the virology diagnostic with electron microscopy; and the use of the statistics for the data analysis. The microbial findings has been: pathogenics bacteria (31.7%), fungus (17%), parasites (1.2%), rotavirus (16.4%), calicivirus (1.6%), adenovirus and coronavirus (1.6%). The clinics findings are presents like digestive and extra-digestive signs, separated in NOVIGE (and no-diagnosticated) and VIGE groups. The seasonal viral and no-viral distributions are present in fig. 5. There are statistics signification: the NOVIGE in summer period (49%) against the VIGE (12.5%) (p < 0.0003); the VIGE in winter period (87.5%) against the VIGE in summer period (12.5%) (p < 0.0003); the GE aetiology (VIGE and NOVIGE) in associated with age groups (p < 0.0003); the vomits preceding diarrhoea in VIGE was 58% and in NOVIGE (19.5%) (P < 0.001). It has been presented without significative differences all the clinics signs and laboratory examinations; the breeding signs for the younger 2 years group compared with the 2 years older; the age correlation (< and > 2 years) and season (winter-summer) with the 16% for the first in VIGE (62.5% rotavirus); the absence of health systems at the NOVIGE (70%) and with both (29%); and others epidemiology considerations of the sequence. With came to conclusion that in our city: 1. there are VIGE with signficative participation of rotavirus; 2. its distribution are winter and age group, also considering the other age groups and virosis; 3. the NOVIGE may difference at the clinic sign like vomit, between all the possible sintomatology; 4. the principal cause of diarrhoea and the no seasonal distribution are the NOVIGE; 5. there are not a strong relationship of diarrhoea by shortage environmental health in this study; 6. it's possible in Río Cuarto to made a fast and direct virology diagnostic using an electron microscopy.


title: Use of viral vectors for the development of vaccines.

text: The exceptional discoveries of antigen/gene delivery systems have allowed the development of novel prophylactic and therapeutic vaccine candidates. This review highlights various antigen-delivery systems, particularly viral vectors, and assesses the underlying technologies in light of their use against AIDS and malaria. Although such recombinant vectors may face extensive preclinical testing and will possibly have to meet stringent regulatory requirements, some of these vectors may benefit from the profound industrial and clinical experience of the parent vaccine. Most notably, novel vaccines based on live, recombinant vectors may combine the induction of broad, strong and persistent immune responses with acceptable safety profiles.


title: Preventing infectious diseases during and after international adoption.

text: Families of internationally adopted children face risks associated with travel if they pick up their children overseas. Unlike other travelers, they also face risks because of close contact with a child with uncertain infection and vaccination status. Tuberculosis organisms, hepatitis A virus, hepatitis B virus, and measles virus have been transmitted from adopted children to family and community members. Intestinal parasites, Bordetella pertussis, and other infectious disease agents can also be transmitted. Some of these infections may be inapparent or may not manifest in adopted children until many years after the adoption. Increased attention to preventive measures for family members and early diagnosis of infectious diseases in adopted children can reduce transmission of the organisms causing these infections. Those providing health care to families planning international adoption should know about standard pretravel advice, as well as the spectrum of possible infections in adopted children, so that they can protect the health of the travelers and family members and close friends who will welcome the new child into the home.


title: [Emergent viruses: SARS-associate coronavirus and H5N1 influenza virus].

text: Two viral agents with RNA genome are responsible for emerging illnesses: influenza virus A/H5N1 and Severe Acute Respiratory Syndrome virus (SARS). For the diagnosis of SARS virus infection, an epidemiological investigation is necessary to know whether the patient has been exposed to a risk in a country where the SARS virus is circulating or whether the patient had worked in a laboratory handling SARS virus. The detection of SARS virus is possible in various clinical samples (including urine) by viral culture or RT-PCR. The handling of those samples and RNA extraction must be performed in a BSL3 laboratory. The SARS virus RT-PCR is poorly sensitive, therefore the test should be performed on samples collected consecutively for several days. In front of a suspicion of A/H5N1, similar procedures are recommended. An epidemiologic investigation is necessary to specify whether the patient stayed in a country where A/H5N1 virus was circulating. Clinical samples needed for a specific diagnosis are: nasopharyngeal, throat-swab or fecal samples, cerebrospinal fluid and blood. The presence of A/H5N1 virus is confirmed by viral isolation or RNA detection by RT-PCR. RNA extraction must be performed in a BSL3 laboratory. For diagnosis of A/H5N1 virus infection, RT-PCR test amplifies specifically a fragment of H5 gene (Hemagglutinin). In french laboratories of medical virology, procedures are ready to diagnose the first case of A/H5N1 virus infection and cases of reemerging SARS virus infection.


title: Evidence of partial protection against foot-and-mouth disease in cattle immunized with a recombinant adenovirus vector expressing the precursor polypeptide (P1) of foot-and-mouth disease virus capsid proteins.

text: A recombinant live vector vaccine was produced by insertion of cDNA encoding the structural proteins (P1) of foot-and-mouth disease virus (FMDV) into a replication-competent human adenovirus type 5 vaccine strain (Ad5 wt). Groups of cattle (n = 3) were immunized twice, by the subcutaneous and/or intranasal routes, with either the Ad5 wt vaccine or with the recombinant FMDV Ad5-P1 vaccine. All animals were challenged by intranasal instillation of FMDV 4 weeks after the second immunizations. In the absence of a detectable antibody response to FMDV, significant protection against viral challenge was seen in all of the animals immunized twice by the subcutaneous route with the recombinant vaccine. The observed partial protection against clinical disease was not associated with a reduction in titre of persistent FMDV infections in the oropharynx of challenged cattle.


title: Attaching and effacing Escherichia coli infection as a cause of diarrhea in young calves.

text: A form of enteric Escherichia coli infection was identified in 60 calves from 59 farming operations. The E coli responsible for these infections principally colonized the colon, inducing a distinctive lesion described as attaching and effacing. Hemorrhagic enterocolitis or blood in the feces was observed on 40% of the farms. Of affected calves, 86.6% were dairy calves (average age, 11.8 days). Forty-four calves were infected concurrently with other enteropathogens (cryptosporidia, rotavirus, coronavirus, enterotoxigenic E coli, bovine viral diarrhea virus, coccidia). Verotoxin-producing E coli was recovered from 31 calves; 8 were serotype O111:NM isolates, 3 were serotype O5:NM, and 1 was serotype O26:NM.


title: New directions for health insurance design: implications for public health policy and practice.

text: National attention on issues of public health preparedness necessarily brings into sharp focus the question of how to assure adequate, community-wide health care financing for preventive, acute care, and long-term medical care responses to public health threats. In the U.S., public and private health insurance represents the principal means by which medical care is financed. Beyond the threshold challenge of the many persons without any, or a stable form of, coverage lie challenges related to the structure and characteristics of health insurance itself, particularly the commercial industry and its newly emerging market of consumer-driven health plans. States vary significantly in how they approach the regulation of insurance and in their willingness to support various types of insurance markets. This variation is attributable to the size and robustness of the insurance market, the political environment, and regulatory tradition and custom. Reconciling health insurance markets with public health-related health care financing needs arising from public health threats should be viewed as a major dimension of national health reform.


title: Globalisation as we enter the 21st century: reflections and directions for nursing education, science, research and clinical practice.

text: The events of September 11th, 2001 in the United States and the Bali bombings of October 2002 are chastening examples of the entangled web of the religious, political, health, cultural and economic forces we experience living in a global community. To view these forces as independent, singular, linearly deterministic entities of globalisation is irrational and illogical. Understanding the concept of globalisation has significant implications not only for world health and international politics, but also the health of individuals. Depending on an individual's political stance and world-view, globalisation may be perceived as an emancipatory force, having the potential to bridge the chasm between rich and poor or, in stark contrast, the very essence of the divide. It is important that nurses appreciate that globalisation does not pertain solely to the realms of economic theory and world politics, but also that it impacts on our daily nursing practice and the welfare of our patients. Globalisation and the closer interactions of human activity that result, have implications for international governance, policy and theory development as well as nursing education, research and clinical practice. Nurses, individually and collectively, have the political power and social consciousness to influence the forces of globalisation to improve health for all. This paper defines and discusses globalisation in today's world and its implications for contemporary nursing education, science, research and clinical practice.


title: Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells.

text: The nucleocapsid (N) protein is the only phosphorylated structural protein of the coronavirus Transmissible gastroenteritis virus (TGEV). The phosphorylation state and intracellular distribution of TGEV N protein in infected cells were characterized by a combination of techniques including: (i) subcellular fractionation and analysis of tryptic peptides by two-dimensional nano-liquid chromatography, coupled to ion-trap mass spectrometry; (ii) tandem mass-spectrometry analysis of N protein resolved by SDS-PAGE; (iii) Western blotting using two specific antisera for phosphoserine-containing motifs; and (iv) confocal microscopy. A total of four N protein-derived phosphopeptides were detected in mitochondria-Golgi-endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-enriched fractions, including N-protein phosphoserines 9, 156, 254 and 256. Confocal microscopy showed that the N protein found in mitochondria-Golgi-ERGIC fractions localized within the Golgi-ERGIC compartments and not with mitochondria. Phosphorylated N protein was also present in purified virions, containing at least phosphoserines 156 and 256. Coronavirus N proteins showed a conserved pattern of secondary structural elements, including six beta-strands and four alpha-helices. Whilst serine 9 was present in a non-conserved domain, serines 156, 254 and 256 were localized close to highly conserved secondary structural elements within the central domain of coronavirus N proteins. Serine 156 was highly conserved, whereas no clear homologous sites were found for serines 254 and 256 for other coronavirus N proteins.


The future character of military medicine.


title: Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)-associated coronavirus infection.

text: To understand the time-course of viraemia and antibody responses to severe acute respiratory syndrome-associated coronavirus (SARS-CoV), RT-PCR and ELISA were used to assay 376 blood samples from 135 SARS patients at various stages of the illness, including samples from patients who were in their early convalescent phase. The results showed that IgM antibodies decreased and became undetectable 11 weeks into the recovery phase. IgG antibodies, however, remained detectable for a period beyond 11 weeks and were found in 100 % of patients in the early convalescent phase. SARS-CoV viraemia mainly appeared 1 week after the onset of illness and then decreased over a period of 1 month, becoming undetectable in the blood samples of the convalescent patients. At the peak of viraemia, viral RNA was detectable in 75 % of blood samples from patients who were clinically diagnosed with SARS 1 or 2 weeks before the test.


title: Nonfatal demyelinating encephalomyelitis induced by coronavirus (JHM strain) infection in mice.

text: C3H mice infected intravenously with the JHM strain of coronavirus showed high incidence of demyelination (44.8%) and low incidence of encephalitis-induced mortality (6.9%). High titers of virus were detectable in the brain and liver of mice only during the first 3 to 12 days of infection (10(3) and 10(4) PFU/g, respectively). Most of the animals recovered from the first phase of disease and some (11.1%) came down with paralysis 6 to 7 weeks after the infection, with no histological changes or virus detectable in their tissues.


title: Serosurvey of ex situ giant pandas (Ailuropoda melanoleuca) and red pandas (Ailurus fulgens) in China with implications for species conservation.

text: Conservation strategies for the giant panda (Ailuropoda melanoleuca) include the development of a self-sustaining ex situ population. This study examined the potential significance of infectious pathogens in giant pandas ex situ. Serologic antibody titers against canine distemper virus (CDV), canine parvovirus (CPV), canine adenovirus (CAV), canine coronavirus (CCV), canine herpesvirus, canine parainfluenza virus (CPIV), Toxoplasma gondii, Neospora caninum, and Leptospira interrogans were measured in 44 samples taken from 19 giant pandas between 1998 and 2003 at the Chengdu Research Base of Giant Panda Breeding in Sichuan, China. Seroassays also included samples obtained in 2003 from eight red pandas (Ailurus fulgens) housed at the same institution. All individuals had been vaccinated with a Chinese canine vaccine that included modified live CDV, CPV, CAV, CCV, and CPIV. Positive antibody titers were found only against CDV, CPV, and T. gondii. Sera were negative for antibodies against the other six pathogens. Results indicate that the quality of the vaccine may not be reliable and that it should not be considered protective or safe in giant pandas and red pandas. Positive antibody titers against T. gondii were found in seven of the 19 giant pandas. The clinical, subclinical, or epidemiologic significance of infection with these pathogens via natural exposure or from modified live vaccines in giant pandas is unknown. Research in this area is imperative to sustaining a viable population of giant pandas and other endangered species.


Serum antibodies to dietary antigens in patients with HIV-1 infection.


title: Opportunistic breast cancer screening in Hong Kong; a revisit of the Kwong Wah Hospital experience.

text: OBJECTIVE To analyse the performance of opportunistic breast screening in local Well Women Clinics during the 5-year period from 1998 to 2002, with reference to international as well as our own earlier experience (1991 to 1993 to 1995). DESIGN Prospective study. SETTING Well Women Clinics in regional Hong Kong hospitals. PARTICIPANTS Women attending the Well Women Clinics of the Tung Wah Group of Hospitals for breast cancer screening. MAIN OUTCOME MEASURES All screening-detected breast cancers. RESULTS After 46 637 screening mammograms and excluding palpable masses detected by the patients themselves, 232 women were detected with cancers, yielding a crude detection rate of 5.0 per 1000. Age range for cancer detection was 35 to 72 (median, 49) years. Clinic staff detected palpable lumps in 83 patients, constituting 36% of the detected cancers, of which 15 (6.5% of all detected cancers) were not identified by mammography. The cancer detection rate was 5.9 per 1000 in the age-group 40-49 years and 3.7 per 1000 in those 50 years or older. The cancer detection rate was 58.5 per 1000 in the high-risk group (aged <40 years with positive family history). The minimal cancer detection rate was 2.2 per 1000, representing 45% of all cancers whose pathology was available to us. Ductal carcinoma in situ comprised 28% of all such cancers. Our recall rates were 4.6% for additional views only, 3.3% for ultrasound only, and 2.3% for both. Positive predictive values for abnormal mammograms and biopsies were 4.9% and 26.0%, respectively. CONCLUSION Mammographic screening has been reported to reduce mortality up to 35% in western countries. However, data concerning Asian Chinese populations are meagre. Our Well Women Clinics pioneered large-scale self-referred breast screening in Hong Kong. Despite the lower incidence of breast cancers than in Occidental populations, our screening programme performed comparably to those in the West, and has improved over time. Our screening service for self-referred women detected breast cancers even at an early stage, which facilitated a better prognosis and more treatment options, whilst appearing to be highly acceptable to our community. Besides, it could provide training and expertise in breast radiology and mammography, which are essential prerequisites for establishing population screening.


title: High-dose hydrocortisone reduces expression of the pro-inflammatory chemokines CXCL8 and CXCL10 in SARS coronavirus-infected intestinal cells.

text: Clinical observations and our high-density oligonucleotide microarray results demonstrated increased expression of proinflammatory chemokines after SARS-CoV infection. Here, we investigated the influence of SARS-CoV infection on CXCL8 (interleukin 8) and CXCL10 (interferon-gamma-inducible protein 10) in human intestinal epithelial (Caco2) cells. RT-PCR and ELISA showed time-dependent up-regulation of both chemokines after SARS-CoV infection. Electric mobility shift assay revealed increased DNA binding activity of the cellular transcription factors activator protein 1 (AP-1) and nuclear factor (B (NF-kappaB) in SARS-CoV infected cells. High hydrocortisone concentrations (> or =50 microg/ml) completely prevented increased DNA binding activity of AP-1 and NF-kappaB and inhibited up-regulation of CXCL8 and CXCL10, but did not reduce chemokine expression to basal levels. Ribavirin that does not inhibit SARS-CoV replication in Vero cells inhibited SARS-CoV replication in Caco2 cells at therapeutical concentrations. Hydrocortisone neither influenced SARS-CoV titres alone nor in combination with ribavirin. Our results show that corticosteroids may be of limited benefit in the suppression of chemokine production by SARS-CoV-infected cells.


title: A quantitative evaluation of fluid leakage around a polyvinyl chloride tapered endotracheal tube cuff using an in-vitro model.

text: INTRODUCTION This study was designed to quantitatively evaluate the sealing effect of a polyvinyl chloride tapered endotracheal tube cuff and to compare the tapered cuff with cylindrical endotracheal tube cuffs using an in vitro viscous fluid model. METHODS Five types of 8.0 mm inner diameter endotracheal tubes (TaperGuard, PortexSacett, PortexSoftseal, Sheridan HVT, Sheridan CF) were fixed in vertically placed 20mm internal diameter acrylic tubes. The cuffs were inflated to 25 mmHg pressure and water was added to the top of the cuff. The amount of water leaking around the cuff at five minutes was measured. Afterwards a viscous fluid was poured above the cuff and the amount of fluid passing around the cuff at five minutes and four hours was measured. Each determination was repeated five times and the data analyzed. RESULTS The median (range) amount (ml) of dyed water passing around the cuff at 5 minutes was TaperGuard tube 0 (0-0.2), PortexSacett 81.1 (44.6-107.9), PortexSoftseal 95.4 (91.4-113.7), Sheridan HVT 46.5 (32.7-74.6) and Sheridan CF 52.6 (31.9-62.2), suggesting that TaperGuard significantly (P<0.05) reduced fluid leakage. The viscous fluid leakage at 5 minutes was not significantly different among the groups while the amount of leaked viscous fluid at 4 hours was 0.2 (0-1.1) for the TaperGuard, 57.6 (11.9-117.4) for the PortexSacett, 23.2 (13.8-33.0) for the PortexSoftseal, 5.5 (2.7-15.4) for the Sheridan HVT and 5.6 (1.8-7.9) for the Sheridan CF. CONCLUSION An endotracheal tube with a tapered polyvinyl chloride cuff had significantly less fluid leakage compared to four tubes with cylindrical cuffs.


title: Interferon induction by several strains of avian infectious bronchitis virus, a coronavirus, in chickens.

text: Eight U.S. and Japanese strains of avian infectious bronchitis virus (IBV) were tested for their interferon-inducing ability in chickens. All strains induced interferon (IFN) in several organs of six-week-old SPF chickens. However, the extent of IFN formation in these chickens was not necessarily the same from one strain to another.


title: The Biology of Persistent Infection: Inflammation and Demyelination following Murine Coronavirus Infection of the Central Nervous System.

text: Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of humans. Although causes of MS are enigmatic, underlying elements contributing to disease development include both genetic and environmental factors. Recent epidemiological evidence has pointed to viral infection as a trigger to initiating white matter damage in humans. Mouse hepatitis virus (MHV) is a positive strand RNA virus that, following intracranial infection of susceptible mice, induces an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. Immune cell infiltration into the central nervous system is critical both to quell viral replication and instigate demyelination. Recent efforts by our laboratory and others have focused upon strategies capable of enhancing remyelination in response to viral-induced demyelination, both by dampening chronic inflammation and by surgical engraftment of remyelination - competent neural precursor cells.


title: A process evaluation of an intervention to improve respiratory infection control practices in family physician offices.

text: OBJECTIVE To conduct a process evaluation of a short-term intervention by public nurses for physicians to facilitate the incorporation of new respiratory infection control practices in physicians' offices. DESIGN Process evaluation. SETTING Family physician offices in Ottawa, Ontario, Canada. PARTICIPANTS Five public health nurse-facilitators and 53 primary care practices including 143 family physicians. METHOD Effectiveness of facilitator training assessed by self-administered questionnaires. Data assessing process of facilitation collected through activity logs and narrative reports. Physicians' satisfaction assessed by post-intervention questionnaire. MAIN FINDINGS Facilitators reported that training strongly contributed to their knowledge and skills and all were either satisfied or highly satisfied with their facilitation training. All practices received at least two visits by the facilitator and more than half (51%) were visited three or more times. Facilitators identified the provision of the evidence-based Tool Kit and consensus-building with office staff as key factors contributing to the intervention's success. Of the 45% of physicians who completed the questionnaire (65/143), only 5% reported being somewhat dissatisfied with the intervention, 11% reported the visits were not frequent enough, and 9% thought the visits were too close together. The majority (97%) felt the facilitation program should be available to all family physicians and 98% would continue to use the service if available. CONCLUSIONS It is feasible for public health nurses to be trained in outreach facilitation to improve respiratory infection control practices in physicians' offices and this has been widely appreciated by physicians. This model of public health/primary care collaboration deserves further exploration.


title: Attitudes of health professionals towards the response to the COVID-19 pandemic in Maghreb.

text: OBJECTIVE Measuring the attitudes of health professionals in two Maghreb countries (Tunisia and Algeria) with regard to the response to COVID-19 during the first quarter of 2020. METHODS This scoping study was based on a "Google Form" covering three constituents of the response plan against COVID-19: responders, activities and crisis communication. The attitudes of health professionals who are working in Tunisia and Algeria were measured through the Likert scale with four propositions, grouped in pairs, during the analysis. RESULTS The study population consisted of 280 health professionals, 170 of whom are Tunisians along with 110 Algerians. The medians of age and that of professional seniority are, respectively, 37 and 10 years. The role of "health workers", "Mass Media" and "civil society associations" was found to be satisfactory according, respectively, to 92%, 71%, and 55% of the respondents. As far as 72% of health professionals are concerned, the "barrier measures" were respected by the population. Approximately, seven in ten respondents were satisfied with the quality of communication occuring between the Ministries of Health and its epidemiological structures. CONCLUSION Health professionals of the Maghreb working in Tunisia and Algeria had a generally positive perception of the role of population responders, community engagement, and the quality of official communication in regards to the response plan against COVID- 19. This perception would be a prerequisite for the success of community participation and multisectoral action as well as essential in the strategy of prevention and control of this pandemic and of possible other health emergencies.


title: Coronavirus IBV: virus retaining spike glycopolypeptide S2 but not S1 is unable to induce virus-neutralizing or haemagglutination-inhibiting antibody, or induce chicken tracheal protection.

text: Avian infectious bronchitis coronavirus (IBV) inactivated by beta-propiolactone induced partial protection of the trachea in up to 40% of chickens following one intramuscular inoculation 4 to 6 weeks prior to challenge. Retention of an intact tracheal ciliated epithelium 4 days after challenge was the criterion of protection. There was no correlation between protection and serum titres of virus-neutralizing (VN) and haemagglutination-inhibiting (HI) antibody, which were maximal at about 4 weeks after inoculation. Virus from which the S1 but not the S2 (spike-anchoring) spike glycopolypeptide had been removed by urea did not induce protection or VN or HI antibody. Four intramuscular inoculations of monomeric S1 induced VN and HI antibody in two and four chickens respectively. These results indicate that VN and HI antibodies are induced primarily by S1, that intact spikes are a major requirement for the induction of protective immunity and that this property is probably associated with S1.


title: Antibodies to Coronavirus OC 43 strain in the population of North-Eastern Hungary.

text: Monthly 120 serum samples were collected from healthy and clinically ill residents of North-Eastern Hungary in the years 1980 and 1981. Haemagglutination-inhibiting antibody to the strain Coronavirus OC 43 was detected in 58% of the 2881 samples. The rate of positive sera was the lowest, 23%, between 7 and 11 months of age and reached the peak of 70% between 15 and 19 years. It did not rise further with age. Paired sera was tested from 405 patients suffering from various diseases. A titre rise was shown in 23 patients; 12 of these were suffering from acute respiratory disease, another 7 showed simultaneous exacerbation of bronchial asthma or spastic bronchitis.


title: The human bocavirus role in acute respiratory tract infections of pediatric patients as defined by viral load quantification.

text: The major objective of this study was to investigate the pathogenic role of human bocavirus (hBoV) in patients hospitalized with acute respiratory tract infection (ARTI). Overall, 685 respiratory samples from 426 patients were examined by PCR for human bocavirus, as well as for other known human respiratory viruses. HBoV was quantified by PCR. Forty/283 (14.1%) pediatric patients, and 2/143 (1.4%) adult patients were found to harbor hBoV for a total of 45 episodes (16 detected as single infection, and 29 as coinfection) of hBoV-associated respiratory infection. HBoV DNA quantification revealed the presence of an NPA viral load > 1.0 x 10(5) DNA copies/ml in respiratory secretions from 17/40 (42.5%) children and 0/2 adults. Below this cut-off, hBoV appeared to be an innocent bystander or a persistent virus. Although hBoV may be frequently detected in children with upper or lower ARTI, in less than 50% young patients it appears to be potentially pathogenic.


title: Talking about public health: developing America's "second language".

text: The mission of public health--improving the health of populations--is difficult to advance in public discourse because a language to express the values animating that mission has not been adequately developed. Following on the work of Robert Bellah, Dan Beauchamp, and others, we argue that the first "language" of American culture is individualism. A second American language of community--rooted in egalitarianism, humanitarianism, and human interconnection--serves as the first language of public health. These values resonate with many Americans but are not easily articulated. Consequently, reductionist, individualistic understandings of public health problems prevail. Advancing the public health approach to the nation's health challenges requires invigorating America's second language by recognizing the human interconnection underlying the core social justice values of public health.


title: The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39).

text: The complete genomic nucleotide sequence (29.7kb) of a Hong Kong severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) strain HK-39 is determined. Phylogenetic analysis of the genomic sequence reveals it to be a distinct member of the Coronaviridae family. 5' RACE assay confirms the presence of at least six subgenomic transcripts all containing the predicted intergenic sequences. Five open reading frames (ORFs), namely ORF1a, 1b, S, M, and N, are found to be homologues to other CoV members, and three more unknown ORFs (X1, X2, and X3) are unparalleled in all other known CoV species. Optimal alignment and computer analysis of the homologous ORFs has predicted the characteristic structural and functional domains on the putative genes. The overall nucleotides conservation of the homologous ORFs is low (<5%) compared with other known CoVs, implying that HK-39 is a newly emergent SARS-CoV phylogenetically distant from other known members. SimPlot analysis supports this finding, and also suggests that this novel virus is not a product of a recent recombinant from any of the known characterized CoVs. Together, these results confirm that HK-39 is a novel and distinct member of the Coronaviridae family, with unknown origin. The completion of the genomic sequence of the virus will assist in tracing its origin.


title: [Disseminated infection by M. tuberculosis complex in patient with IFN-γ receptor 1 complete deficiency].

text: BACKGROUND Several mutations have been described leading to impaired immunity in the IL-12/IFN-γ axis and, they confer susceptibility to mycobacterial infections. One of the more serious clinical phenotypes is secondary to mutations at IFN-γ receptor 1 gene, characterized by an early onset and more severe disease. CLINICAL REPORT We present a 3-month-old female patient with systemic M. tuberculosis complex who has a homozygous mutation, it affects the splicing site at IFNGR1 c.201-1G> T. At time of this report, she is with antimycobacterial treatment in the protocol of pluripotent hematopoietic cell transplantation (TCHP). CONCLUSION It has been reported that antiphimic treatment should be maintained until the immune system is restored by the TCHP. If patients receive THCP before the age of 1 year old, they have a better prognosis. Diminish the levels of IFN-γ in plasma before the procedure is associated to better results.


title: History of protein crystallography in China.

text: China has a strong background in X-ray crystallography dating back to the 1920s. Protein crystallography research in China was first developed following the successful synthesis of insulin in China in 1966. The subsequent determination of the three-dimensional structure of porcine insulin made China one of the few countries which could determine macromolecular structures by X-ray diffraction methods in the late 1960s and early 1970s. After a slow period during the 1970s and 1980s, protein crystallography in China has reached a new climax with a number of outstanding accomplishments. Here, I review the history and progress of protein crystallography in China and detail some of the recent research highlights, including the crystal structures of two membrane proteins as well as the structural genomics initiative in China.


title: Lower respiratory viral infections in immunocompetent children.

text: Viral lower respiratory disease causes a heavy burden on our society. Better understanding of the epidemiology of these viruses combined with new rapid diagnostic techniques will provide more rapid and more reliable diagnosis of these agents in the future. Two agents not commonly thought of as causes of LRI in children (rhinoviruses, coronaviruses) should now be added to an already long list. Effective drugs exist for prophylaxis against influenza virus type A and therapy for influenza virus type A, type B, and RSV. While no new antiviral drugs are near clinical use at this time, new antiviral agents are constantly being tested and developed. High-titer, specific antiviral IVIG appears promising for both therapy and prophylaxis. Over the next decade, improved influenza virus vaccines and safe and effective vaccines against HPIV and RSV are expected. Adenoviral vaccines for use in immunocompromised patients are possible, but a generally available vaccine for all children is less likely. Although the basic clinical epidemiology of these viruses has been well investigated over the last 30 years, new molecular techniques are greatly expanding our understanding of these agents. Antigenic and genetic variation is being found in many viruses previously thought homogeneous. The exact role and biologic significance of this variation is just beginning to be explored, but already there is evidence of differences in pathogenicity and immunogenicity in many of these substrains. All of this information will have an impact on future vaccine and antiviral drug development.


title: Immunomodulatory effects of a traditional Chinese medicine with potential antiviral activity: a self-control study.

text: Traditional Chinese medicine (TCM) has been used for prevention and treatment of severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in spring 2003. We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases. Thirty-seven healthy volunteers were given the oral TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days 0, 15 and 29 for hematology, biochemistry and immunology tests, including the measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1 and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated in a control study without TCM treatment for the same time course of blood tests. Two volunteers withdrew on day 2, due to headache and dizziness. All others remained well without any side effects. No participants showed significant changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio increased significantly from 1.31 +/- 0.50 (mean +/- SD) on day 0 to 1.41 +/- 0.63 on day 15 (p < 0.02), and reduced to 1.32 +/- 0.47 on day 29 (p < 0.05). In the control study, there were no changes in the CD4/CD8 ratio. The transient increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the administration of the innovative TCM may have beneficial immunomodulatory effects for preventing viral infections including SARS.


title: Requirements for CEACAMs and cholesterol during murine coronavirus cell entry.

text: Previous reports have documented that cholesterol supplementations increase cytopathic effects in tissue culture and also intensify in vivo pathogenicities during infection by the enveloped coronavirus murine hepatitis virus (MHV). To move toward a mechanistic understanding of these phenomena, we used growth media enriched with methyl-beta-cyclodextrin or cholesterol to reduce or elevate cellular membrane sterols, respectively. Cholesterol depletions reduced plaque development 2- to 20-fold, depending on the infecting MHV strain, while supplementations increased susceptibility 2- to 10-fold. These various cholesterol levels had no effect on the binding of viral spike (S) proteins to cellular carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors, rather they correlated directly with S-protein-mediated membrane fusion activities. We considered whether cholesterol was indirectly involved in membrane fusion by condensing CEACAMs into "lipid raft" membrane microdomains, thereby creating opportunities for simultaneous binding of multiple S proteins that subsequently cooperate in the receptor-triggered membrane fusion process. However, the vast majority of CEACAMs were solubilized by cold Triton X-100 (TX-100), indicating their absence from lipid rafts. Furthermore, engineered CEACAMs appended to glycosylphosphatidylinositol anchors partitioned with TX-100-resistant lipid rafts, but cells bearing these raft-associated CEACAMs were not hypersensitive to MHV infection. These findings argued against the importance of cholesterol-dependent CEACAM localizations into membrane microdomains for MHV entry, instead suggesting that cholesterol had a more direct role. Indeed, we found that cholesterol was required even for those rare S-mediated fusions taking place in the absence of CEACAMs. We conclude that cholesterol is an essential membrane fusion cofactor that can act with or without CEACAMs to promote MHV entry.


Scientists for a better world.


title: The NS5A protein of the hepatitis C virus genotype 1a is cleaved by caspases to produce C-terminal-truncated forms of the protein that reside mainly in the cytosol.

text: The nonstructural 5A (NS5A) protein of the hepatitis C virus (HCV) is a multifunctional protein that is implicated in viral replication and pathogenesis. We report here that NS5A of HCV-1a is cleaved at multiple sites by caspase proteases in transfected cells. Two cleavage sites at positions Asp154 and 248DXXD251 were mapped. Cleavage at Asp154 has been previously recognized as one of the caspase cleavage sites for the NS5A protein of HCV genotype 1b (1, 2) and results in the production of a 17-kDa fragment. The sequence 248DXXD251 is a novel caspase recognition motif for NS5A and is responsible for the production of a 31-kDa fragment. Furthermore, we show that Arg217 is implicated in the production of the previously described 24-kDa product, whose accumulation is affected by both calpain and caspase inhibitors. We also showed that caspase-mediated cleavage occurs in the absence of exogenous proapoptotic stimuli and is not related to the accumulation of the protein in the endoplasmic reticulum. Interestingly, our data indicate that NS5A is targeted by at least two different caspases and suggest that caspase 6 is implicated in the production of the 17-kDa fragment. Most importantly, we report that, all the detectable NS5A fragments following caspase-mediated cleavage are C-terminal-truncated forms of NS5A and are mainly localized in the cytosol. Thus, in sharp contrast to the current view we found no evidence supporting a role for caspase-mediated cleavage in the transport of the NS5A protein to the nucleus, which could lead to transcriptional activation.


ACP Journal Club. Graduated compression stockings did not prevent deep venous thrombosis after stroke and increased skin complications.


title: Public health investigations required for protecting the population against novel coronaviruses.

text: ABSTRACT There have been many laboratory-based investigations since the emergence of the novel coronaviruses in the autumn of 2012, but most of the parameters required for establishing scientifically the control measures that will protect against them have yet to be determined. Equally, the global distribution of the viruses in their animal reservoir has yet to be established. The experience of investigating and controlling another novel coronavirus, SARS, in 2003 shows how national and local investigations can come together as an international coalition and successfully avert epidemics. A menu of studies that need to be undertaken, especially in the countries experiencing transmission, is presented here.


title: A severe acute respiratory syndrome-associated coronavirus-specific protein enhances virulence of an attenuated murine coronavirus.

text: Most animal species that can be infected with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical disease, hindering studies of pathogenesis. To develop an alternative system for the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells, indicating that SARS-CoV proteins function in the context of a heterologous coronavirus infection. Furthermore, these results suggest that the attenuated murine coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine coronaviruses cause a reproducible and well-characterized clinical disease, offer virtually no risk to laboratory personnel, and should be useful for elucidating the role of SARS-CoV nonstructural proteins in viral replication and pathogenesis.


COVID-19: "You're gonna need a bigger boat".


title: [Etiological, epidemiological and clinical aspects of coronavirus infection MERS-CoV].

text: All medical staff and travellers to the Arabian Peninsula should be aware of a new epidemic caused by Middle East respiratory syndrome coronavirus (MERS-CoV), which has emerged in the Arabian Peninsula (2012), secondary cases have been seen in Africa, Europe, Asia and the United States. It seems likely that the outbreak will continue with sporadic adventive cases occurring outside the Middle East, including Poland. Polish medical literature on MERS-CoV is rather scant. Therefore, the article describes etiology, epidemiology, symptoms and diagnostic methods of MERS-CoV infection which are available in Poland. Selected cases of patients infected with MERS-CoV are also presented followed by preventive methods. Comparisons between MERS-CoV and SARS-CoV are briefly described. Epidemiological and genetic studies point at zoonotic transmission of MERS-CoV from camels and possibly bats. Infection is characterized by severe acute respiratory failure with a high fatality rate and the ability to spread from person to person; health care-associated outbreaks have been described. No known vaccine or antiviral therapy has been developed for MERS. The diagnosis is made by demonstrating the MERS-CoV in lower respiratory secretions by RT PCR. General hygiene measures such as regular hand washing before and after touching animals and avoiding contact with sick animals in the epidemic areas, should be adhered to. Health-care workers should always apply standard precautions consistently with all patients, regardless of their diagnosis due to non-specific symptoms of MERS-CoV in the early stage of infection.


Guidance for Health Care Providers on Management of Cardiovascular Complications in Patients Suspected or Confirmed with COVID 19 Virus Infection.


title: The time course of the immune response to experimental coronavirus infection of man.

text: After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.


title: Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses.

text: Recombination is increasingly seen as an important means of shaping genetic diversity in RNA viruses. However, observed recombination frequencies vary widely among those viruses studied to date, with only sporadic occurrences reported in RNA viruses with negative-sense genomes. To determine the extent of homologous recombination in negative-sense RNA viruses, phylogenetic analyses of 79 gene sequence alignments from 35 negative-sense RNA viruses (a total of 2154 sequences) were carried out. Powerful evidence was found for recombination, in the form of incongruent phylogenetic trees between different gene regions, in only five sequences from Hantaan virus, Mumps virus and Newcastle disease virus. This is the first report of recombination in these viruses. More tentative evidence for recombination, where conflicting phylogenetic trees were observed (but were without strong bootstrap support) and/or where putative recombinant regions were very short, was found in three alignments from La Crosse virus and Puumala virus. Finally, patterns of sequence variation compatible with the action of recombination, but not definitive evidence for this process, were observed in a further ten viruses: Canine distemper virus, Crimean-Congo haemorrhagic fever virus, Influenza A virus, Influenza B virus, Influenza C virus, Lassa virus, Pirital virus, Rabies virus, Rift Valley Fever virus and Vesicular stomatitis virus. The possibility of recombination in these viruses should be investigated further. Overall, this study reveals that rates of homologous recombination in negative-sense RNA viruses are very much lower than those of mutation, with many viruses seemingly clonal on current data. Consequently, recombination rate is unlikely to be a trait that is set by natural selection to create advantageous or purge deleterious mutations.


title: Pestivirus infections in ruminants in Norway.

text: Serological surveys in Norway have demonstrated neutralising antibodies against bovine virus diarrhoea (BVD) virus in cattle, sheep and goats. The prevalences were 18.5%, 4.5% and 3.6%, respectively. Occurrence of pestivirus-induced disease in Norway is described. Outbreaks of reproductive failure and mucosal disease have been reported, and the number of persistently-infected animals detected has increased considerably in recent years. Acute BVD occurs rarely. Border disease (BD) in sheep, first diagnosed in 1981, has subsequently been demonstrated sporadically. In goats, typical BD was diagnosed in 1982, with three later occurrences of reproductive failure. Experimental infections in pregnant goats induced a high rate of severe foetopathogenic effect. Signs and lesions in offspring were comparable to ovine BD. Similar findings were demonstrated in goats given a pestivirus-contaminated vaccine. In newborn kids, experimental infection had an adverse influence on growth and health. Persistent infection in goats is probably rare.


title: Severe acute respiratory syndrome (SARS): imaging findings during the acute and recovery phases of disease.

text: Severe acute respiratory syndrome (SARS) is a new form of atypical pneumonia, which has become a major health crisis in East Asia and Canada, with the potential for becoming the next worldwide epidemic. Until the validation of diagnostic kits is completed, clinical findings, contact history, and radiologic findings are the key to diagnosis of this disease. The imaging findings on conventional radiographs and computed tomography (CT) in the acute phase as well as during recovery are presented.


title: [Development and application of a safe SARS-CoV neutralization assay based on lentiviral vectors pseudotyped with SARS-CoV spike protein].

text: The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike protein (S) is a major target for neutralizing antibody. To develop and apply a safe neutralization assay for SARS-CoV, lentiviral SARS-CoV S pseudotypes had been constructed based on a three plasmid system, which contained pVRC8304 (harboring codon optimized full-length SARS-CoV S protein), pCMV delta 8. 2 (HIV-1 gag/pol construct) and pHR'CMV EGFP (the green fluorescent protein reporter construct). The pseudo-typed lentiviral particles were used to develop an in vitro microneutralization assay that was both sensitive and specific for SARS-CoV neutralizing antibody. We used this assay to determine the titers of the neutralizing antibodies (Nabs) in serum samples from mice immunized with various rVVs expressing different S fragments of SARS-CoV. The serum antibodies derived from S and various segments of S1 region neutralized SARS-CoV in vitro. No cross-neutralization occurred with the goat antiserum prepared with inactivated HCoV-OC43 or HCoV-229E. Neutralization titers measured by this assay were highly parallel with those measured by the assay using live SARS-CoV. Because the pseudotype assay does not require handling live SARS virus, it is a useful tool to determine serum neutralizing titers during natural infection and the preclinical evaluation of candidate vaccines.


title: The life aquatic.

text: If we want to know for sure whether there was, or still is, life on Mars, we have to send people there.


title: Diary.

text: Our roundup of what's on.


How SARS changed the world in less than six months.


Synthesis of subgenomic RNAs by positive-strand RNA viruses.


title: [Twin girls infected with SARS-CoV-2].

text: This article reports the diagnosis and treatment of twin girls who were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Hunan Province, China. The twin girls, aged 1 year and 2 months, were admitted on January 29, 2020 due to fever for one day and cough and sneezing for two days respectively. Both recovered after symptomatic treatment. The two girls had mild symptoms and rapid recovery, suggesting that children with SARS-CoV-2 infection may be mild and have a good prognosis. There were differences in the clinical symptoms and imaging findings between the twin girls, suggesting that SARS-CoV-2 infection has diverse clinical features in children.


title: Therapeutic potential of Toll-like receptor 9 activation.

text: In the decade since the discovery that mouse B cells respond to certain unmethylated CpG dinucleotides in bacterial DNA, a specific receptor for these 'CpG motifs' has been identified, Toll-like receptor 9 (TLR9), and a new approach to immunotherapy has moved into the clinic based on the use of synthetic oligodeoxynucleotides (ODN) as TLR9 agonists. This review highlights the current understanding of the mechanism of action of these CpG ODN, and provides an overview of the preclinical data and early human clinical trial results using these drugs to improve vaccines and treat cancer, infectious disease and allergy/asthma.


title: Comparison of different antigen preparations as substrates for use in passive hemagglutination and enzyme-linked immunosorbent assays for detection of antibody against bovine enteric coronavirus.

text: Purified coronavirus, detergent extracts of purified coronavirus, and virus-infected Madin-Darby bovine kidney cells were evaluated as antigen substrates in enzyme-linked immunosorbent assay (ELISA) and passive hemagglutination systems. Only detergent-extracted and -unextracted, purified viruses were reactive as antigen substrates in ELISA, whereas all three antigen preparations could be used for sensitization of erythrocytes in the passive hemagglutination assay. The passive hemagglutination system with infected cell extracts exhibited a similar level of sensitivity and specificity to the ELISA system employing purified coronavirus but enabled 300 times more tests to be performed per volume of virus-infected cell culture.


Imported cutaneous melioidosis in traveler, Belgium.


title: Role of viruses and bacteria in acute wheezy bronchitis in childhood: a study of sputum.

text: Sputum, nasal swabs, and throat swabs were obtained from 22 children aged between 5 and 15 years during 72 attacks of wheezy bronchitis. A virus, most commonly a rhinovirus, was isolated in 49% of all episodes and in 64% of 22 severe episodes requiring treatment with corticosteroids; the isolation rate was higher early in the illness than later. Virus was recovered more often from sputum than from the nose or throat, suggesting that viral replication occurs freely in the lower respiratory tract: the cytological findings in sputum were compatible with an inflammatory response to viral infection. Pathogenic bacteria appeared to play a minor role compared with viruses, and routine antibiotic treatment was probably of little value in moost cases. The significance of the results is discussed in relation to the pathogenesis of childhood wheezy bronchitis.


title: Virus Infection and Titration of SARS-CoV in Mouse Lung.

text: Two critical steps when investigating an animal model of a virus infection are consistently successfully infecting animals and accurately determining viral titers in tissue throughout the course of infection. Here we discuss in detail how to infect mice with SARS-CoV and then quantify the titer of virus in the lung.


title: An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion.

text: In recent years, a great deal of research has been conducted to identify genetic polymorphisms. One focus has been to characterize variability in metabolic enzyme systems that could impact internal doses of pharmaceuticals or environmental pollutants. Methods are needed for using this metabolic information to estimate the resulting variability in tissue doses associated with chemical exposure. We demonstrate here the use of physiologically based pharmacokinetic (PBPK) modeling in combination with Monte Carlo analysis to incorporate information on polymorphisms into the analysis of toxicokinetic variability. Warfarin and parathion were used as case studies to demonstrate this approach. Our results suggest that polymorphisms in the PON1 gene, that give rise to allelic variants of paraoxonase, which is involved in the metabolism of paraoxon (a metabolite of parathion), make only a minor contribution to the overall variability in paraoxon tissue dose, while polymorphisms in the CYP2C9 gene, which gives rise to allelic variants of the major metabolic enzyme for warfarin, account for a significant portion of the overall variability in (S)-warfarin tissue dose. These analyses were used to estimate chemical-specific adjustment factors (CSAFs) for the human variability in toxicokinetics for both parathion and warfarin. Implications of alternatives in the calculation of CSAFs are explored. Key decision points for applying the PBPK-Monte Carlo approach to evaluate toxicokinetic variability for other chemicals are also discussed.


Infection control in times of Ebola: how well are we training the next generation of intensivists in Australia and New Zealand?


title: DNA probe for the human coronavirus OC43 also detects neonatal calf diarrhea coronavirus (NCDCV).

text: Human coronaviruses (HCV) OC43 and 229E are the second most frequently isolated agents of common colds, and have also been associated with severe upper respiratory infections in children and with gastroenteritis of unknown etiology, such as infantile necrotizing enterocolitis. While HCV-OC43 and neonatal calf diarrhea coronavirus NCDCV cannot be held responsible for enteric infection in man, serological data suggest the possible existence of a human coronavirus, antigenically related to HCV-OC43 and NCDCV, and responsible for enteric infections. We developed a rapid and sensitive method for the diagnosis of the human respiratory coronavirus infections, and for detecting these viruses in suspect coronavirus infections. This assay entails a reverse transcriptase polymerase chain reaction, followed by Southern blot analysis with a probe specific for the amplification products.


title: [Did you say vulnerable populations ?]

text: The current new coronavirus pandemic has highlighted the importance of taking into consideration population groups particularly at risk of contracting Covid-19 disease or developing severe forms of the disease. The medical literature, the press and the authorities have thus stepped up the use of the expression « vulnerable populations » in recent weeks to refer to it. However, behind this general expression there are diverse but often interdependent realities whose specific consideration and understanding seem essential for the effective management of the epidemic and its health and socio-economic consequences.


title: The public health enterprise: examining our twenty-first-century policy challenges.

text: This paper examines the public health enterprise and its policy challenges in the twenty-first century. Among the many challenges public health faces, we include here collaboration across a broad range of stakeholders, the public health infrastructure, agreement on public health's essential services, preparedness, accountability and measurement, workforce and a research agenda. Two Institute of Medicine reports on the future of public health have set the context for a more in-depth review of the public health workforce and infrastructure. Policy advocates must ask, however, why, if the way and the means are so clear, the public health system is still in disarray.


title: Chronic eosinophilic dermatitis associated with persistent feline herpes virus infection in cheetahs (Acinonyx jubatus).

text: A chronic ulcerative and eosinophilic dermatitis occurred in 20 captive cheetahs (Acinonyx jubatus) with persistent feline herpes virus 1 (FHV1) infection. Affected animals had erythematous, ulcerated plaques primarily on the face and forelegs in sites of contact with lachrymal and salivary secretions. The dermatitis was characterized by dense infiltrates of eosinophils and plasma cells and pseudoepitheliomatous hyperplasia. Rare keratinocytes within the lesions had nuclei with marginated chromatin and small eosinophilic inclusions composed of herpes virus nucleocapsids. Virus isolated from lesions was confirmed to be FHV1. Lesions persisted and progressed unless removed by cryoexcision. The occurrence of this unusual reaction to FHV1 in approximately 5% of captive North American cheetahs suggests a species propensity for a Th2-dominant response to herpes virus infection. This atypical immune reaction may indicate a heritable trait or modulation of the immune response by other factors such as chronic stress.


title: Influenza: current evidence and informed predictions.

text: Every winter there are sharp rises in medical visits, hospitalizations and deaths from acute respiratory illness worldwide. Influenza is an important cause of these and is the only common viral respiratory pathogen with licensed vaccines available that are safe and effective in preventing disease. Over 50 countries have national vaccination programs focusing on the elderly population and those at high risk. In the USA, healthy children are also now offered the vaccine; routine immunization of the young, who are similarly vulnerable to hospitalization as the old, is likely to become universal. There remains a need for further improvement in vaccine effectiveness (both in the short- and long-term), vaccine administration and compliance. Recent technological developments raise the prospect of using new vaccine types, such as live attenuated and Vero cell-cultured vaccines, that are easier to administer and may induce broader immunity.


Immunogenetic programs for viral induction of mucous cell metaplasia.


Engaging the international community during the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea.


Tackling the next influenza pandemic.


Use of nonradioactive cDNA probes to differentiate porcine respiratory coronavirus and transmissible gastroenteritis virus isolates.


title: Coronavirus JHM OMP1 pathogenesis in owl monkey CNS and coronavirus infection of owl monkey CNS via peripheral routes.

text: Two separate studies are described in this report. First, 5 Owl monkeys were inoculated intracerebrally (IC) with coronavirus JHM OMP1; this virus isolate was cultured from the brain of an animal inoculated with uncloned MHV JHM. Two of the animals became neurological impaired and were sacrificed; these animals had developed severe encephalomyelitis as previously described. Two of the remaining 3 healthy animals were inoculated IC again at 90 days post-inoculation (DPI) and all 3 were sacrificed approximately 5 months after the first virus inoculation. Despite the lack of detectable infectious virus, viral RNA and antigen, all 3 animals had significant white matter inflammation and areas of demyelination in the spinal cord. In the second study 4 Owl monkeys were inoculated intranasally (IN) and ocularly and 4 inoculated intravenously (i.v.) with JHM OMP1. The animals were sacrificed between 16 and 215 DPI with 2 IN and 2 i.v. animals receiving a second i.v. inoculum at 152 DPI. Viral RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. One of the animals that received the second inoculum developed neurological impairment and subsequent analysis of tissues showed viral antigen in both brain and spinal cord. Viral products were predominantly found in blood vessels suggesting hematogenous spread with entry into the central nervous system (CNS) through endothelium.


title: Comparative Study of Performance in Ultrasonic Tissue Dissection for Sleeve Gastrectomy: Wired versus Cordless.

text: BACKGROUND The sleeve gastrectomy is being performed increasingly as a primary procedure for the treatment of morbid obesity. A minimally invasive approach is currently applied to the procedure. The two major steps are dissection and stapling. For dissection, several tools have been developed. The goal of this study was to compare the efficiency and the ergonomics of two ultrasonic devices during the sleeve gastrectomy. MATERIALS AND METHODS Thirty patients were randomised for the use of a cordless Sonicision™ (Covidien, Mansfield, MA) or a cord-containing HARMONIC ACE®+ (Ethicon Endo-Surgery Inc., Cincinnati, OH) during dissection. Both devices were assessed for objective and subjective measures. RESULTS There was no significant difference in duration of the procedures. The assembly and installation time of the Sonicision™ were significantly shorter; however, the dismantle time was not. No difference in plume formation or dissection failures was found between the devices. Scrub nurses scored the Sonicision™ significantly clearer and easier in use and more reliable. The surgeons, however, did not find one of the devices easier in use, more reliable or precise, but they did report better manoeuvrability of the Sonicision™. CONCLUSION In comparison to the wired HARMONIC ACE®+, during sleeve gastrectomy, the cordless Sonicision™ was considered easier to use, faster during assembling and installation, and more reliable with better manoeuvrability. Surgeons scored both devices equally effective. Both ultrasonic devices can be used easily and safely for a sleeve gastrectomy.


title: Prone Position in Management of COVID-19 Patients; a Commentary.

text: SARS-CoV-2 virus causes a pneumonia that was identified through fever, dyspnea, and acute respiratory symptoms and named COVID-19. This disease exacerbates in a number of patients and causes pulmonary edema, multi-organ failure, and acute respiratory distress syndrome (ARDS). Prevalence of ARDS among COVID-19 patients has been reported to be up to 17%. Among the introduced treatment methods for management of ARDS patients, prone position can be used as an adjuvant therapy for improving ventilation in these patients. Here we reviewed the literature regarding the role of prone position in management of COVID-19 patients.


title: Hepatocellular carcinoma in captive slender tailed meerkats (Suricata suricatta): 5 cases.

text: Hepatocellular carcinoma was diagnosed in five slender tailed meerkats (Suricata suricatta) housed at the Smithsonian Institution's National Zoological Park between 1980 and 2013. Animals included four females and one male, ranging from 7 to 15 yr of age. Common clinical signs included weight loss and lethargy. Three of the neoplasms originated from the right medial liver lobe and were located adjacent to or partially incorporated in the gall bladder. Three animals had solitary masses, and two animals had multiple hepatic masses; all were characterized by polygonal to round neoplastic hepatocytes arranged in a trabecular pattern with smaller regions of varied solid, adenoid, and rarely peliod cell patterns. Hemorrhage and necrosis often with cystic degeneration was noted in all five cases. There was no evidence of metastatic disease in any of the cases examined.


Infectious diseases. Hungry for details, scientists zoom in on SARS genomes.


The race to outpace severe acute respiratory syndrome (SARS).


title: Local renin-angiotensin II systems, angiotensin-converting enzyme and its homologue ACE2: their potential role in the pathogenesis of chronic obstructive pulmonary diseases, pulmonary hypertension and acute respiratory distress syndrome.

text: Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, local renin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability to act as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. In the present paper, we review data from studies of the past decade that implicate AngII and functional polymorphisms of the ACE gene that increase ACE activity with increased susceptibility for asthma and chronic obstructive pulmonary disease (COPD) and for pulmonary hypertension. Moreover, drugs that inhibit the synthesis of AngII (ACE inhibitors) or that antagonize its actions on its receptors (Angiotensin II receptor blockers -ARBs) have been shown to provide beneficial effects. Another recent discovery reviewed is the presence of a homologue of ACE, ACE2, which cleaves a single amino acid from AngII and forms a heptapeptide with vasodilatory actions, Ang 1-7. The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE and ACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally, mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.


title: Probing the structure of the SARS coronavirus using scanning electron microscopy.

text: A novel coronavirus, SARS-CoV, has been confirmed to be the aetiological agent of SARS. Transmission electron microscope (TEM) images played an important role in initial identification of the pathogen. In order to obtain greater morphological detail of SARS-CoV than could be obtained by TEM, we used ultra-high resolution scanning electron microscopy (SEM) to image the virus particles. We show here the three-dimensional appearance of SARS-CoV. Enhanced detail of the ultrastructure reveals the trimeric structure of the 10-20 nm spikes on the virion surface. These results contribute to characterization of the SARS agent and development of new antiviral strategies.


title: Severe Acute Respiratory Syndrome (SARS): loud clang of the Leper's bell.

text: Severe acute respiratory syndrome (SARS) or the "Chinese Chernobyl" emerged against an alarming background of rising infectious disease in poor rural China and to a backdrop of interregional and global polarization of population well-being and vulnerability. SARS has added its own dissonant note to "health disturbance", caused fear and panic and disrupted international commerce. Its emergence should be perceived as a disturbing alarm that underscores the need to strengthen public health and facilitate construction of a human security "umbrella" in the event of future disasters. Although SARS has produced a relatively insignificant level of damage when compared to other threats, its long-term effects on health should not be underestimated, based on its unexpected appearance and still unknown properties. This essay presents a qualitative flowchart that follows SARS from its origin in China to the accumulation of global damage. Two future scenarios were formulated, covering a worse-case outcome and containment outcome, which currently appears to be the case. In the event of the worst-case scenario it is doubtful whether any health service in Europe could cope. In either case, the development of a European Union Center for Disease Control is mandatory.


title: Typing of field isolates of infectious bronchitis virus based on the sequence of the hypervariable region in the S1 gene.

text: A universal primer set was developed that amplifies a region covering hypervariable region (HVR) 1 and HVR 2 in the S1 gene of the infectious bronchitis virus (IBV). The universality of this primer set was confirmed by testing the reference strains of different serotypes or variants of the IBV present in the United States. An approximately 450-bp region containing HVR 1 and HVR 2 of 7 untyped field isolates obtained in 1999 and 2000 was amplified. Direct sequencing followed by phylogenetic analysis on that region allowed us to type those field isolates that were not typable by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Furthermore, it was found that typing by phylogenetic analysis of that region correlates with virus neutralization results. Together with RT-PCR and RFLP, this method will serve as a fast typing method for IBV diagnosis.


title: Transient disorder in dynamically growing networks.

text: When a certain "seed" disturbance begins to spread on a large network, the number of nodes infected is a function of time. Regarding the set of infected nodes as constituting a dynamic network that evolves continuously in time, we ask: how does the order in the collective dynamics of the network vary with time? Utilizing synchronizability as a measure of the order, we find that there exists a time at which a maximum amount of disorder corresponding to a minimum degree of synchronizability can arise before the system settles into a more ordered steady state. This phenomenon of transient disorder occurs for networks of both regular and complex topologies. We present physical analyses and numerical support to establish the generality of the phenomenon.


title: Viral infections in free-living populations of the European wildcat.

text: While the importance of viral infections is well studied in domestic cats, only limited information is available on their occurence and prevalence in the European wildcat (Felis silvestris silvestris). The aim of this study was to determine the prevalence of antibodies to feline coronavirus (FCoV), calicivirus (FCV), herpesvirus (FHV), parvovirus (FPV), immunodeficiency virus (FIV), leukemia virus (FeLV), and FeLV antigenemia in 51 European wildcat sera. Samples were collected between 1996 and 1997 from wildcat populations in France, Switzerland, and Germany. Antibodies to FCoV were detected in two cats (4%) and FCoV RNA was detected in feces of one of these two cats. Antibodies to FCV, FHV and FPV were found at relatively low frequencies of 16%, 4%, and 2%, respectively. Antibodies to FIV were not detected. Although antigen and antibodies to FeLV were detected in 49%, and 75%, respectively, no evidence of FeLV-associated pathology was found. From the low prevalence of FCoV, FCV, FHV and FPV infections and from the fact that the European wildcats live solitarily, it was concluded that these viral infections do not spread readily within a population. Therefore, it may be assumed that release into the wild of European wildcats bred in captivity would not bring about a high risk of introducing of these viral infections to the free-ranging wildcats. As an exception, wildcats should be tested for absence of FIV infection before release if they were at risk to acquire this infection from domestic cats.


title: A system for study of coronavirus mRNA synthesis: a regulated, expressed subgenomic defective interfering RNA results from intergenic site insertion.

text: A system that exploits defective interfering (DI) RNAs of mouse hepatitis virus (MHV) for deciphering the mechanisms of coronavirus mRNA transcription was developed. A complete cDNA clone of MHV DI RNA containing an inserted intergenic region, derived from the area of genomic RNA between genes 6 and 7, was constructed. After transfection of the in vitro-synthesized DI RNA into MHV-infected cells, replication of genomic DI RNA as well as transcription of the subgenomic DI RNA was observed. S1 nuclease protection experiments, sequence analysis, and Northern (RNA) blotting analysis revealed that the subgenomic DI RNA contained the leader sequence at its 5' end and that the body of the subgenomic DI RNA started from the inserted intergenic sequence. Two subgenomic DI RNAs were synthesized after inserting two intergenic sites into the MHV DI RNA. Metabolic labeling of virus-specific protein in DI RNA replicating cells demonstrated that a protein was translated from the subgenomic DI RNA, which can therefore be considered a functional mRNA. Transfection study of gel-purified genomic DI RNA and subgenomic DI RNA revealed that the introduction of the genomic DI RNA, but not subgenomic DI RNA, into MHV-infected cells was required for synthesis of the subgenomic DI RNA. A series of deletion mutations in the intergenic site demonstrated that the sequence flanking the consensus sequence of UCUAAAC affected the efficiency of subgenomic DI RNA transcription and that the consensus sequence was necessary but not sufficient for the synthesis of the subgenomic DI RNA.


title: Coronavirus spike glycoprotein, extended at the carboxy terminus with green fluorescent protein, is assembly competent.

text: Due to the limited ultrastructural information about the coronavirion, little is known about the interactions acting at the interface between nucleocapsid and viral envelope. Knowing that subtle mutations in the carboxy-terminal endodomain of the M protein are already lethal, we have now probed the equivalent domain of the spike (S) protein by extending it terminally with a foreign sequence of 27 kDa: the green fluorescent protein (GFP). When expressed individually in murine cells, the S-GFP chimeric protein induced the formation of fluorescent syncytia, indicating that it was synthesized and folded properly, trimerized, and transported to the plasma membrane, where it exhibited the two key S protein functions, i.e., interaction with virus receptor molecules and membrane fusion. Incorporation into virus-like particles demonstrated the assembly competence of the chimeric spike protein. The wild-type S gene of mouse hepatitis coronavirus (MHV) was subsequently replaced by the chimeric construct through targeted recombination. A viable MHV-SGFP was obtained, infection by which could be visualized by the fluorescence induced. The efficiency of incorporation of the chimeric protein into particles was, however, reduced relative to that in wild-type particles which may explain, at least in part, the reduced infectivity produced by MHV-SGFP infection. We conclude that the incorporation of spikes carrying the large GFP moiety is apparently impaired by geometrical constraints and selected against during the assembly of virions. Probably due to this disadvantage, deletion mutants, having lost the foreign sequences, rapidly evolved and outcompeted the chimeric viruses during virus propagation. The fluorescent MHV-SGFP will now be a convenient tool to study coronaviral cell entry.


title: Canine Circovirus 1 (CaCV-1) and Canine Parvovirus 2 (CPV-2): Recurrent Dual Infections in a Papillon Breeding Colony.

text: Recurrent outbreaks of sudden death and bloody diarrhea were reported in March 2013 and February 2014 in a breeding colony of Papillon dogs. During the first outbreak, 1 adult dog and 2 eight-month-old puppies died. During the second outbreak, 2 ten-week-old puppies died. One puppy from the first outbreak and 2 puppies from the second outbreak were examined at necropsy. Histologically, all 3 puppies had severe segmental crypt necrosis of the small intestine and marked lymphoid follicle depletion in the spleen and Peyer's patches. Real-time (RT) polymerase chain reaction (PCR) demonstrated abundant canine parvovirus (CPV-2) DNA (Ct<15) in the affected small intestine, and immunohistochemistry detected large amounts of CPV-2 antigen in intestinal crypt epithelium and Kupffer cells but few positive macrophages in lymphoid organs. All puppies had marked sinusoidal histiocytosis and multifocal granulomatous inflammation in mesenteric lymph nodes and spleen, prompting additional RT-PCR testing for canine circovirus 1 (CaCV-1). Very high levels of CaCV-1 DNA (Ct<13) were detected in small intestine, lymph nodes, and spleen. In situ hybridization for CaCV-1 detected rare positive nuclei of regenerating crypt epithelium but abundant amounts of CaCV-1 nucleic acid in the cytoplasm and nuclei of histiocytes in all lymphoid tissues, including granulomatous inflammatory foci and hepatic Kupffer cells. Significant levels of CaCV-1 DNA were detected in blood and serum (Ct as low as 13) but not feces from 3 surviving dogs at 2 months or 1 year after the outbreak, respectively. We hypothesize that CPV-2 infection predisposed dogs to CaCV-1 infection and ultimately resulted in more severe clinical disease.


title: The coronaviruses.

text: Coronaviruses of human origin have emerged as probable important etiologic agents of acute upper respiratory tract illnesses in adults; their role in the etiology of respiratory illnesses of childhood is less certain. The first coronavirus of human origin, B814, was described in 1965 and since that time only 31 additional strains have been recovered. Ten of these were originally recovered in human embryonic tracheal organ culturesonly, and the remainder in monolayer cell cultures. All of the latter group were antigenically related to a prototype strain designated 229e. As a result of the fastidious growth requirements of these agents, most of the knowledge concerning the clinical syndromes associated with them has come from chajlenge studies in volunteers and seroepidemiologic investigations. Coronaviruses have been shown to be associated with a substantial number of adult respiratory illnesses especially during certain periods when rhinovirus infections are infrequent. Progress in propagating coronaviruses and in detecting coronavirus infections has been achieved recently: viruses similar to 229E were successfully recovered in human embryonic intestine cell cultures from patients with upper respiratory tract illnesses; 30C strains (B814, LP and EVS) were recovered in L132 cell cultures from infectious nasal washings; OC43(and OC38) viruses which were originally recovered in OC and later adapted to grow in suckling mice were not only shown to directly hemagglutinate various erythrocytes but were also adapted to grow in MK cell cultures; OC43 virus was also found to induce hemadsorption of rat and mouse erythrocytes in certain cell cultures; and a coronavirus strain was detected by immune electron microscopy. Coronaviruses are also associated with certain diseases in animals.


title: Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques.

text: There are currently no nonhuman primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that six common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. In this study, we employ complementary DNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa-DPA, -DPB, -DQA, -DQB, -DRA, and -DRB loci on the six common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci including DPA, a locus thought to be monomorphic in rhesus macaques. Similar to other Old World monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other nonhuman primates. The characterization of these full-length-expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines, tetramers, and other molecular reagents that can be used to explore CD4+ T lymphocyte responses in MCM.


Surgical Procedures and Short-Term Outcomes of a Complete Laparoscopic Colectomy with Intracorporeal Anastomosis for Right-Sided Colon Cancer.


title: Factors associated with the psychological impact of severe acute respiratory syndrome on nurses and other hospital workers in Toronto.

text: OBJECTIVES A survey was conducted to measure psychological stress in hospital workers and measure factors that may have mediated acute traumatic responses. METHODS A self-report survey was completed by 1557 healthcare workers at three Toronto hospitals in May and June 2003. Psychological stress was measured with the Impact of Event Scale. Scales representing attitudes to the outbreak were derived by factor analysis of 76 items probing attitudes to severe acute respiratory syndrome. The association of Impact of Event Scale scores to job role and contact with severe acute respiratory syndrome patients was tested by analysis of variance. Between-group differences in attitudinal scales were tested by multivariate analysis of variance. Attitudinal scales were tested as factors mediating the association of severe acute respiratory syndrome patient contact and job role with total Impact of Event Scale by linear regression. RESULTS Higher Impact of Event Scale scores are found in nurses and healthcare workers having contact with patients with severe acute respiratory syndrome. The relationship of these groups to the Impact of Event Scale score is mediated by three factors: health fear, social isolation, and job stress. CONCLUSIONS Although distress in response to the severe acute respiratory syndrome outbreak is greater in nurses and those who care for patients with severe acute respiratory syndrome, these relationships are explained by mediating variables that may be available for interventions to reduce stress in future outbreaks. In particular, the data suggest that the targets of intervention should include job stress, social isolation, and health fear.


title: Clinical prognostic rules for severe acute respiratory syndrome in low- and high-resource settings.

text: BACKGROUND An accurate prognostic model for patients with severe acute respiratory syndrome (SARS) could provide a practical clinical decision aid. We developed and validated prognostic rules for both high- and low-resource settings based on data available at the time of admission. METHODS We analyzed data on all 1755 and 291 patients with SARS in Hong Kong (derivation cohort) and Toronto (validation cohort), respectively, using a multivariable logistic scoring method with internal and external validation. Scores were assigned on the basis of patient history in a basic model, and a full model additionally incorporated radiological and laboratory results. The main outcome measure was death. RESULTS Predictors for mortality in the basic model included older age, male sex, and the presence of comorbid conditions. Additional predictors in the full model included haziness or infiltrates on chest radiography, less than 95% oxygen saturation on room air, high lactate dehydrogenase level, and high neutrophil and low platelet counts. The basic model had an area under the receiver operating characteristic (ROC) curve of 0.860 in the derivation cohort, which was maintained on external validation with an area under the ROC curve of 0.882. The full model improved discrimination with areas under the ROC curve of 0.877 and 0.892 in the derivation and validation cohorts, respectively. CONCLUSION The model performs well and could be useful in assessing prognosis for patients who are infected with re-emergent SARS.


title: The use of Permacol™ mesh in contaminated complex abdominal wall defects.

text: The repair of complex abdominal wall defects in contaminated fields often presents a dilemma for general surgeons. Synthetic mesh, although strong, may lead to chronic infection or even visceral erosion. Leaving the abdomen open presents challenges for ward management and delays definitive care, as well as allowing the musculature to retract over time. Numerous biological mesh alternatives have arisen over the previous decade, which may make primary closure in this setting a practical alternative, although durability may prove the downside. Here we present our local experience with PermacolTM mesh (Porcine Acellular Dermal Matrix - PADM; Covidien, Mansfield, MA) in four challenging cases and discuss the role this relatively new mesh may have for these and other applications.


title: A retrospective clinical review of extracellular matrices for tissue reconstruction: equine pericardium as a biological covering to assist with wound closure .

text: Complex wounds frequently undergo surgical excision and grafting in an attempt to optimize the wound environment and to facilitate wound closure. Individuals who have not responded to conventional non-surgical therapies and dressings may not be good candidates for autologous grafting. A fully flexible, cross-linked, acellular equine pericardium biological xenograft was used to address difficult-to-treat and recalcitrant wounds of the lower extremity. Twenty-four complex wounds of varying etiology, including diabetic, venous, trauma, vasculitic, and post-surgical wounds underwent surgical debridement and xenograft application. The individual results were reviewed in a retrospective study over an 18-month period. The duration of the wounds ranged between 3 months to 2 years. The average time to wound closure was 5.96 weeks. The median time to closure was 6 weeks. No significant adverse events were noted. The data review suggests the use of equine pericardium as a xenograft and biological cover may significantly benefit patients with difficult-to-heal wounds. Additional animal and clinical studies are in progress to help understand the mechanism of action of the xenograft in the clinical environment.


title: Endovascular management of giant middle cerebral artery aneurysms.

text: BACKGROUND This article reported the experience of endovascular treatment in giant middle cerebral artery (MCA) aneurysms with parent artery occlusion or stent-assisted coiling. MATERIAL AND METHODS Eleven consecutive patients with giant MCA aneurysms were included. The aneurysms predominantly involved the M1 segment in two cases, bifurcation in four cases, and M2 in five cases. Four M2 fusiform aneurysms were treated with parent artery sacrifice after balloon occlusion test. The seven unruptured aneurysms and one ruptured one were treated with stent-assisted coiling. The post-operation and long-term follow-up angiographic and clinical outcomes were analyzed. RESULTS Endovascular coiling was performed successfully in all 11 cases. All four M2 fusiform cases using parent artery occlusion strategy achieved complete occlusion of aneurysms. In the seven cases with stent-assisted coiling, four were completely occluded, two were partially occluded and one remained small residue. Mild perioperative complications occurred in six patients. The follow-up angiography taken at a mean of 13.5 months of eight patients showed that seven aneurysms remained stable or improved and one M1 aneurysms relapsed and needed further treatment. CONCLUSION Stent-assisted coiling or parent artery occlusion of selected giant MCA aneurysms is an option to consider.


SARS and occupational health in the air.


title: [Epidemiological perspectives on SARS and avian influenza].

text: SARS is a respiratory infection caused by Coronavirus (Nidoviruses, RNA) from which 3 groups are known. Group 1 affects dogs, cats, pigs, and the human agent is 229 E. Group 2 affects bovines or rodents, and the human agent is OC43. And group 3 corresponds to the avian pathology.... The epidemics emerged on February 2003 in Guangdong, South China, due to consumption of exotic animals (Civeta, etc.), and it spread through interperson contagion to other regions in Asia, America and Europe. Incubation period is about 2-7 days. Transmission Of the virus is person-to person, but also by excretions and residual water. Basic reproductive rate is 2 to 4, and it is considered that 2.7 persons are infected from the initial case. In June 2003, SARS affected over 8,000 people and 774 were killed. Mortality approaches to 10%, and it is higher among older people rising up to 50% in those aged over 65 years. It is important to quickly establish action protocols regarding clinical, epidemiological and prevention aspects. Avian influenza is an infection caused by type A Influenza Orthomixovirus, in which migration birds and wild ducks are the main reservoir. Avian viruses correspond to H5, H7, H9. In 1997 it was observed that type AH5N1 jumped interspecies barrier and affected 18 humans, and 6 of them died. At the end of 2003 and in 2004 this type of poultry flu was described in Asia. FAO has emphasized that sacrifice of chicken in affected farms is the most effective measure to fight against the disease. It has also been established suppression of imports from these countries. There is no evidence on interperson contagion from chicken contagion, nor on food-borne contagion to humans.


title: The effects of processing inhibitors of N-linked oligosaccharides on the intracellular migration of glycoprotein E2 of mouse hepatitis virus and the maturation of coronavirus particles.

text: We have studied the effects of tunicamycin and inhibitors of the processing of N-linked glycans including N-methyl-1-deoxynojirimycin, castanospermine, mannodeoxynojirimycin, and swainsonine on the transport of glycoprotein E2 and the intracellular maturation of the coronavirus mouse hepatitis virus A59. Indirect immunofluorescence staining with monoclonal antibodies revealed that glycoprotein E2 exhibits different antigenic properties depending on the presence and on the structure of the N-linked oligosaccharides and that efficient transport of glycoprotein E2 to the plasma membrane requires the removal of glucose residues. In the presence of tunicamycin in the nonglycosylated E2 apoprotein was synthesized in normal amounts and readily acylated throughout the infectious cycle. This E2-species could not be detected on the surface of mouse hepatitis virus A59-infected cells with indirect immunofluorescence staining or lactoperoxidase labeling. N-Methyl-1-deoxynojirimycin and castanospermine, both of which selectively inhibited the processing glucosidases, caused a drop in virion formation by two log steps and a drastic delay in the surface expression of glycoprotein E2. The E2 species synthesized under such conditions was acylated but accumulated intracellularly in a compartment distinct from the Golgi. Concomitantly, synthesis of the matrix glycoprotein E1 of mouse hepatitis virus A59 was drastically impaired. Mannodeoxynojirimycin and swainsonine, which block later stages of the processing pathway, had less or no effect on the transport of glycoprotein E2 and the formation of virus particles.


Physician mobility in Canada.


title: Analysis on the co-localization of asbestos bodies and Fas or CD163 expression in asbestos lung tissue by in-air micro-pixe.

text: To prevent and control disease caused by exposure to various agents, it is necessary to determine the harmful level of intervention and to establish a method for measuring that level. In-air microparticle-induced X-ray emission (in-air micro-PIXE) analysis is based on irradiation of specimens with a proton ion microbeam, and has been modified for biological application. Two-dimensional analysis and quantitative analysis using the system confirmed that asbestos induced apoptosis by upregulating Fas expression and also revealed the accumulation of CD163-expressing macrophages in the lungs of patients with asbestosis. By quantitative comparison of the area of Fas or CD163 expression and the Fas- or CD163-negative area in asbestos lung tissue, the harmful levels which caused the expression of Fas or CD163 could be estimated on Silica, Ferrous iron, and Magnesium (the components of asbestos) deposition. These results indicate that the system could be useful for investigating the pathogenesis of inhaled particle-induced immune reactions and for determining harmful levels of exogenous agents.


title: Interactions between the cytoplasmic proteins and the intergenic (promoter) sequence of mouse hepatitis virus RNA: correlation with the amounts of subgenomic mRNA transcribed.

text: Previous studies suggested that coronavirus RNA transcription involves interaction between leader RNA and the intergenic (IG) sequences, probably via protein-RNA interactions (X. M. Zhang, C.-L. Liao, and M. M. C. Lai, J. Virol., 68:4738-4746, 1994; X. M. Zhang and M. M. C. Lai, J. Virol., 68:6626-6633, 1994). To determine whether cellular proteins are involved in this process, we performed UV cross-linking experiments using cytoplasmic extracts of uninfected cells and the IG (promoter) sequence between genes 6 and 7 (IG7) and the 5' untranslational region of mouse hepatitis virus genomic RNA. We demonstrated that three different cellular proteins (p70, p48, and p35/38) bound to the promoter sequence of the template RNA. Deletion analyses of the template RNA mapped the binding site of p35/38 at the consensus transcription initiation signal. In contrast, the binding of p70 and p48 was less specific. p35/38 is the same protein as the one previously identified to bind to the complementary strand of the leader RNA; its binding affinity to the leader was approximately 15 times stronger than that to IG7. Site-directed mutagenesis of the IG sequence revealed that mutations in the consensus sequence of IG7 (UCUAAUCUAAAC to UCGAAAC and GCUAAAG), which resulted in reduced subgenomic mRNA transcription, also caused correspondingly reduced levels of p35/38 binding. These results demonstrated that the extent of protein binding to the IG sequences correlated with the amounts of subgenomic mRNAs transcribed from the IG site. These studies suggest that these RNA-binding proteins are involved in coronavirus RNA transcription and may represent transcription factors.


title: Presence of genomic polyadenylate and absence of detectable virion transcriptase in human coronavirus OC-43.

text: Human coronavirus RNA, prepared by extraction of purified virions with phenol-chloroform, consists of a major 15 to 55S class and a minor 4S class of RNA fragments. Polyadenylic acid [poly (A)] sequences are present in 15 to 55S but not in 4S RNA, suggesting different functions for each class. A stretch of poly (A) of approximately 19 adenosine monophosphate residues was obtained in sizing experiments after digesting OC-43 RNA with pancreatic and T1 ribonucleases. An OC-43 virion RNA transcriptase could not be detected with systems optimal for detecting the transcriptases of influenza and Newcastle disease virus.


Severe acute respiratory syndrome: What have we learned two years later?