title: Advances in awareness monitoring technologies.

text: PURPOSE OF REVIEW Initial studies suggested that the use of processed electroencephalogram technology could significantly decrease the incidence of unintended intraoperative awareness events during general anesthesia. Subsequent work has cast doubts on these findings. This review will examine the current state of awareness monitoring. RECENT FINDINGS Recently published randomized controlled trials examining the use of the bispectral index during general anesthesia have not been able to show superiority over other forms of monitoring depth of anesthesia, such as end-tidal anesthetic-agent concentration. Additionally, there is current interest in utilizing the unprocessed electroencephalogram to ascertain depth of anesthesia and recent studies have demonstrated its use in preventing postoperative delirium. SUMMARY Although awareness monitors such as the bispectral index monitor may have benefit in patients in whom volatile anesthetic agents must be minimized - such as in hemodynamically unstable patients, or patients undergoing total intravenous anesthesia - these monitors do not appear to be useful for all patients.


title: Comorbidity and multimorbidity in patients with schizophrenia and bipolar disorder: similarities and differencies.

text: BACKGROUND There is a need for better understanding and research of the comorbidity structure in schizophrenia and bipolar disorder. OBJECTIVE To assess the prevalence of somatic and psychiatric comorbidity in schizophrenia and bipolar affective disorder treated at the University Hospital Centre Zagreb. METHOD This retrospective study compares the prevalence of comorbid diagnosis of somatic and psychiatric disorders in 192 patients with schizophrenia and 97 patients with bipolar disorder. The diagnoses were established according to ICD-10 criteria. The data were collected from hospital medical documentation. RESULTS Patients with bipolar disorder had more both somatic (67.1% vs. 50.6%) and psychiatric (29.9% vs. 10.9%) comorbidity than patients with schizophrenia. The three most prevalent somatic comorbidites in patients with bipolar disorders were cardiovascular (22.6%), endocrinological (22.6%), and gastrointestinal (16.4%) disorders while neurological (11.4%), gastrointestinal (10.9%) and endocrinological (9.3%) disorders were the most frequent in patients with schizophrenia. CONCLUSION The exact prevalence and nature of the somatic and psychiatric comorbidity in patients with schizophrenia and bipolar disorder is still unclear and further research is needed.


title: Evidence for a porcine respiratory coronavirus, antigenically similar to transmissible gastroenteritis virus, in the United States.

text: A respiratory variant of transmissible gastroenteritis virus (TGEV), designated PRCV-Ind/89, was isolated from a swine breeding stock herd in Indiana. The virus was readily isolated from nasal swabs of pigs of different ages and induced cytopathology on primary porcine kidney cells and and on a swine testicular (ST) cell line. An 8-week-old pig infected oral/nasally with the respiratory variant and a contact pig showed no signs of respiratory or enteric disease. These pigs did not shed virus in feces but did shed the agent from the upper respiratory tract for approximately 2 weeks. Baby pigs from 2 separate litters (2 and 3 days old) also showed no clinical signs following oral/nasal inoculation with PRCV-Ind/89. In a third litter, 5 of 7 piglets (5 days old) infected either oral/nasally or by stomach tube developed a transient mild diarrhea with villous atrophy. However, virus was not isolated from rectal swabs or ileal homogenates of these piglets, and viral antigen was not detected in the ileum by fluorescent antibody staining even though the virus was easily recovered from nasal swabs and lung tissue homogenates. Swine antisera produced against PRCV-Ind/89 or enteric TGEV cross-neutralized either virus. In addition, an anti-peplomer monoclonal antibody, 4F6, that neutralizes TGEV also neutralized the PRCV-Ind/89 isolate. Radioimmunoassays with a panel of monoclonal antibodies indicated that the Indiana respiratory variant and the European PRCV are antigenically similar.


title: SARS: current knowledge and management.

text: Severe acute respiratory syndrome (SARS) was identified as a new infectious disease in Asia early in 2003. Since then an unprecedented global public health response has been mounted. This article describes current knowledge of the infection and outlines the management of SARS in the UK.


title: A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope.

text: HIV-1 entry into cells is mediated by the envelope glycoprotein receptor-binding (gp120) and membrane fusion-promoting (gp41) subunits. The gp41 heptad repeat 1 (HR1) domain is the molecular target of the fusion-inhibitor drug enfuvirtide (T20). The HR1 sequence is highly conserved and therefore considered an attractive target for vaccine development, but it is unknown whether antibodies can access HR1. Herein, we use gp41-based peptides to select a human antibody, 5H/I1-BMV-D5 (D5), that binds to HR1 and inhibits the assembly of fusion intermediates in vitro. D5 inhibits the replication of diverse HIV-1 clinical isolates and therefore represents a previously unknown example of a crossneutralizing IgG selected by binding to designed antigens. NMR studies and functional analyses map the D5-binding site to a previously identified hydrophobic pocket situated in the HR1 groove. This hydrophobic pocket was proposed as a drug target and subsequently identified as a common binding site for peptide and peptidomimetic fusion inhibitors. The finding that the D5 fusion-inhibitory antibody shares the same binding site suggests that the hydrophobic pocket is a "hot spot" for fusion inhibition and an ideal target on which to focus a vaccine-elicited antibody response. Our data provide a structural framework for the design of new immunogens and therapeutic antibodies with crossneutralizing potential.


title: Mount Sinai Hospital dental program for persons with disabilities: role in undergraduate dental education.

text: Access to dental care for persons with special needs or disabilities continues to be a problem. This population is known to have a high incidence of dental disease, but unfortunately oral health is a significant unmet health need in many cases. To address this need, the Mount Sinai Hospital Dental Program for Persons with Disabilities was developed over 30 years ago by staff within the discipline of pediatric dentistry at the faculty of dentistry of the University of Toronto. Undergraduate students receive hands-on clinical training in dental management of persons with disabilities, the majority of whom have a developmental disability and could receive care in a community-based dental practice. This program has been successful, but access to community care is still an issue for the population served. Two new initiatives have been introduced in an attempt to develop personal links between persons with disabilities and future dentists, the first a series of lectures given by persons with disabilities and the second a nonprofit organization dedicated to raising awareness of the need for dental care for persons with disabilities. Among other activities, the organization sponsors a community-based event called Sharing Smiles Day, which brings together dental students and persons with disabilities in a carnival-like setting where the emphasis is on personal interactions. Dental preventive education is also provided but is of secondary importance. These initiatives and the program as a whole represent recognition of the responsibility of educators to ensure that new graduates have both the education and the desire to provide needed dental care to persons with disabilities.


Not waiting for godot: proactive efforts to find potential zoonotic agents.


title: Effects of different us isolates of porcine reproductive and respiratory syndrome virus (PRRSV) on blood and bone marrow parameters of experimentally infected pigs.

text: Seventy five-week-old, crossbred, caesarean-derived, colostrum-deprived pigs were randomly divided into five groups of 14 pigs and assigned one of five treatments: the intranasal inoculation of 1 (5.7) TCID50 of one of four plaque-purified isolates of porcine reproductive and respiratory syndrome virus (PRRSV) (VR2385, VR2431, ISU-984 and ISU-22), or uninfected cell culture and media. Haematological variables were measured for 21 days and bone marrow was analysed when the pigs were killed three, seven, 10, 21 or 28 days after the inoculation. The PRRSV-infected pigs had non-regenerative anaemia and markedly increased myeloid:erythroid ratios from three to 21 days after inoculation. There was a significant (P < 0.05) difference in the severity of the anaemia induced by the four PRRSV isolates; the most highly pneumovirulent strains (VR2385, ISU-984 and ISU-22) induced more severe anaemia than the least virulent isolate (VR2431). The anaemia induced by PRRSV was probably due to a direct or indirect effect on erythroid precursor cells in the bone marrow.


title: Incidence and cluster occurrence of palatal fistula after furlow palatoplasty by a single surgeon.

text: Fifty-seven cleft palate patients underwent primary repair with Furlow palatoplasty by the same surgeon from January 2001 to January 2005. There were 8 fistulae, 7 of which occurred out of 9 patients treated between July 2003 and January 2004 when operations were resumed after the outbreak of severe acute respiratory syndrome in Hong Kong; 1 minute fistula occurred after this period and closed spontaneously. Longer operation time and higher proportion of Veau classes III and IV clefts were noted in the fistula group. The high incidence and cluster occurrence immediately after SARS could be related to changes in the provision of nursing care and the level of parental supervision, in addition to more difficult operations encountered as reflected by more extensive clefts and longer operation time. We would like to emphasize that expert nursing care and close supervision with the help of parents play a very important role in achieving the best possible clinical outcome from cleft palate surgery in pediatric patients.


Staple Line Bleeding in Sleeve Gastrectomy: a Simple and Cost-Effective Solution.


title: Delayed behavioral effects of postnatal exposure to corticosterone in the zebra finch (Taeniopygia guttata).

text: Early developmental conditions can significantly influence the growth and survival of many animal species. We studied the consequences of exposure to corticosterone (CORT), a stress hormone, during the nestling stage on two behavioral traits (neophobia, social dominance) measured when the birds had reached independence. Nestling zebra finches (Taeniopygia guttata) were exposed twice daily to exogenous CORT via oral administration for a 12-day period up until fledging. Experimental CORT administration depressed nestling growth rates, confirming results previously obtained in this species. Our data on neophobic behavior revealed a significant interaction between sex and treatment, with CORT-dosed males showing reduced latencies to approach a novel object, while there was little effect of corticosterone treatment on female neophobia. There was no significant effect of age (30 or 50 days), however, there was a non-significant trend towards an interaction between treatment and age, with neophobia increasing with age in the CORT-dosed birds, but decreasing in controls. At 50 days of age previous exposure to corticosterone resulted in reduced success in competitions for a non-food-based resource (a perch) in both sexes. There were no effects of brood size on any behavioral traits measured here, but this may be due to the small range in brood size used. Our results show that elevated levels of stress hormones during postnatal development can have significant effects on important behavioral traits, i.e., neophobia and dominance. Moreover, they confirm the importance of rearing conditions in shaping adult phenotypes.


title: Infectious salmon anemia virus specifically binds to and hydrolyzes 4-O-acetylated sialic acids.

text: Infectious salmon anemia virus (ISAV) is the causative agent of infections in farmed Atlantic salmon. ISAV presumably represents a new genus within the Orthomyxoviridae. ISAV has been shown earlier to exhibit a receptor-destroying activity, which was defined as an acetylesterase with unknown specificity. We have analyzed the substrate specificity of the ISAV esterase in detail. Purified ISAV hydrolyzed free 5-N-acetyl-4-O-acetyl neuraminic acid. In addition, the purified 9-O-acetylated sialic acid derivative was also hydrolyzed, but at lower rates. When we used a glycosidically bound substrate, ISAV was unable to hydrolyze 9-O-acetylated sialic acid, which represents the major substrate for the influenza C virus esterase. ISAV completely de-O-acetylated glycoprotein-bound 5-N-acetyl-4-O-acetyl neuraminic acid. Thus, the enzymatic activity of the hemagglutinin-esterase of ISAV is comparable to that of the sialate-4-O-esterases of murine coronaviruses and related group 2 coronaviruses. In addition, we found that ISAV specifically binds to glycoproteins containing 4-O-acetylated sialic acids. Both the ISAV esterase and recombinant rat coronavirus esterase specific for 4-O-acetylated sialic acids hydrolyzed ISAV receptors on horse and rabbit erythrocytes, indicating that this sialic acid represents a receptor determinant for ISAV.


title: Two antigenic groups of human coronaviruses detected by using enzyme-linked immunosorbent assay.

text: Paired sera from volunteers inoculated with one of the five recently isolated strains of human coronavirus (HCV), AD, GI, HO, PA, and RO, none of which has been grown in tissue culture, or with strain OC38 were tested against coronavirus antigens by enzyme-linked immunosorbent assay. When HCV strains OC43, 229E, or the 229E-related tissue culture-adapted strains PR and TO were used as antigens, it was shown that all strains fell into one of two antigenic groups. The HCV OC43 group was comprised of strains OC43, GI, HO, and RO, and the HCV 229E group contained strains AD and PA as well as the tissue culture-adapted strains PR, TO, and KI. Enzyme-linked immunosorbent assay of the paired sera with the coronavirus mouse hepatitis virus strain 3 as antigen confirmed the relationship of this virus to the HCV OC43 group but not to the HCV 229E group.


title: The effectiveness of antibacterial curtains in comparison with standard privacy curtains against transmission of microorganisms in a hospital setting.

text: Studies have shown a correlation between a cleaner patient environment and lower infection rates and reduced risk of transmission. Privacy curtains are potentially important sites of bacterial contamination in hospitals. Privacy curtains integrated with antimicrobial properties have been shown to increase the time to first contamination compared with standard privacy curtains. In this study, we examined the difference in bacterial colonization of different curtains. We experimentally contaminated antibacterial Fantex protective curtains and compared the bacterial counts to natural contamination of privacy curtains. There was a significant reduction in the CFU/cm2 on antibacterial Fantex protective privacy curtains after 24 hours of experimental contamination with Pseudomonas aeruginosa, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA) or extended-spectrum-producing organisms (Escherichia coli or Klebsiella pneumoniae), compared to standard privacy curtains. Levels of environmental contamination with S. epidermis, Streptococcus viridians, E. coli, S. haemolyticus, S. aureus, S. capitis, non-fermenting Gram-negative bacteria, and Bacillus species were also significantly less on the Fantex curtains after two months hanging in the emergency department. Healthcare facilities may find that addressing surfaces, including use of antibacterial privacy curtains, is an effective horizontal strategy for addressing healthcare-associated infections across the board.


Application of reverse transcription polymerase chain reaction to detect porcine epidemic diarrhea virus in Vero cell culture.


title: Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis.

text: We suggest the use of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19). We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesised sequence of events.


Message from the president.


title: Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats.

text: We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo-infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin.


title: Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice.

text: We describe a model of severe acute respiratory syndrome-coronavirus (SARS-CoV) infection in C57BL/6 mice. A clinical isolate of the virus introduced intranasally replicated transiently to high levels in the lungs of these mice, with a peak on day 3 and clearance by day 9 postinfection. Viral RNA localized to bronchial and bronchiolar epithelium. Expression of mRNA for angiotensin converting enzyme 2, the SARS-CoV receptor, was detected in the lung following infection. The virus induced production in the lung of the proinflammatory chemokines CCL2, CCL3, CCL5, CXCL9, and CXCL10 with differential kinetics. The receptors for these chemokines were also detected. Most impressively, mRNA for CXCR3, the receptor for CXCL9 and CXCL10, was massively up-regulated in the lungs of SARS-CoV-infected mice. Surprisingly Th1 (and Th2) cytokines were not detectable, and there was little local accumulation of leukocytes and no obvious clinical signs of pulmonary dysfunction. Moreover, beige, CD1-/-, and RAG1-/- mice cleared the virus normally. Infection spread to the brain as it was cleared from the lung, again without leukocyte accumulation. Infected mice had a relative failure to thrive, gaining weight significantly more slowly than uninfected mice. These data indicate that C57BL/6 mice support transient nonfatal systemic infection with SARS-CoV in the lung, which is able to disseminate to brain. In this species, proinflammatory chemokines may coordinate a rapid and highly effective innate antiviral response in the lung, but NK cells and adaptive cellular immunity are not required for viral clearance.


title: [Large differences in excess mortality in March-May 2020 by country of birth in Sweden].

text: The Swedish strategy for dealing with covid-19 has been criticized for not accounting for difficulties of conducting voluntary social distancing in settings with household overcrowding, dependence on public transport and large proportion of service sector workers. In such neighbourhoods there is typically a larger proportion of immigrants. We compared all-cause-mortality data in Sweden by country of origin from 2020 and 2016-2019 and found large disparities. The number of deaths among persons born in countries from which many refugees have migrated to Sweden in the last decades was 220% higher in March-May 2020 compared to the mean in 2016-2019. In contrast, there was no increased mortality among persons aged 40-64 years and a 19% increased number of deaths of those aged above 65 years born in Sweden, EU or North America during these three months. These observations further illustrate the need for a dedicated and more diverse strategy in dealing with the covid-19 pandemic.


title: Erlotinib-associated near-fatal interstitial pneumonitis in a patient with relapsed lung adenocarcinoma.

text: Erlotinib (Tarceva) is a human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Interstitial lung disease, associated with gefitinib (Iressa) use, has been reported in approximately 1% of patients worldwide. However, the adverse pulmonary effects of erlotinib remain poorly documented. Reviewed English language publications in MEDLINE and PubMed suggest that this report is to be the first case report in English of a histologically-confirmed case of near-fatal interstitial pneumonitis with acute lung injury, associated with erlotinib, in East Asian patients. Physicians are hereby encouraged to promptly evaluate new or worsening pulmonary symptoms so that they can detect early radiographic signs of pulmonary toxicity in patients on erlotinib. If toxicity is confirmed, erlotinib should be discontinued and the patient treated appropriately. The case presented suggests that the outcome of erlotinib-associated pulmonary toxicity with acute respiratory failure may be favorable with adequate early management.


title: Preparing for an influenza pandemic: mental health considerations.

text: There is a common belief that an influenza pandemic not only is inevitable, but that it is imminent. It is further believed by some, and dramatized by a 2006 made-for-television-movie, that such a pandemic will herald an end to life as we know it. Are such claims hyperboles, or does a pandemic represent the most significant threat to public health in the new millennium? Any potential effects of a disease on a population are mediated not only through the pathophysiological mechanisms of the disease itself, but through the psychological and behavioral reactions that such a disease might engender. It is the purpose of this paper to explore the potential psychological and behavioral reactions that may accompany an influenza pandemic.


title: A retrospective study on adverse reactions to canine vaccines in Japan.

text: Adverse reactions to vaccines were examined in 311 canine cases reported to the Ministry of Agriculture, Forestry and Fisheries in Japan during the period of 6 years from April of 1994 to March of 2000, and classified according to their clinical symptoms. There were 27 cases of adverse reactions to rabies virus vaccines. Gastrointestinal symptoms were the most frequently observed (26%), followed by respiratory and/or cardiovascular symptoms (22%) and dermatologic symptoms (11%). There were 284 cases of adverse reactions to non-rabies monovalent vaccines and mixed vaccines. Dermatologic symptoms were the most frequently observed (53%), followed by gastrointestinal symptoms (16%) and respiratory and/or cardiovascular symptoms (14%). Of the total 311 cases, 11 (3.5%) died of adverse reactions to vaccines.


title: Safety is not negotiable: the importance of occupational health and safety to pandemic planning.

text: The 2003 outbreak of severe acute respiratory syndrome, or SARS, generated a great deal of attention around the ability of Canada's health system to respond to a health crisis. This event underscored a very serious reality--on the whole, Canada's health system was not prepared to quickly and efficiently deal with a health emergency. This reality was particularly clear in Canada's largest city, Toronto, as the hospital system was not able to contain the outbreak. Armed with little knowledge of the nature of the threat or epidemiology of the disease, the health system was overwhelmed with how to deal with this crisis. Perhaps of greatest concern, however, was the inability to provide accurate and timely information to health institutions, healthcare workers and the public regarding the appropriate procedures and precautions to ensure optimal safety for all persons and control the spread of disease. This paper makes the case that the integration of occupational health and safety into pandemic planning is key to its success.


title: Persistent infection of cultured cells with mouse hepatitis virus (MHV) results from the epigenetic expression of the MHV receptor.

text: The A59 strain of murine coronavirus mouse hepatitis virus (MHV) can cause persistent infection of 17C1-1 cells and other murine cell lines. Persistently infected cultures released large amounts of virus (10(7) to 10(8) PFU/ml) and were resistant to superinfection with MHV but not to infection with unrelated Semliki Forest and vesicular stomatitis viruses. The culture medium from persistently infected cultures did not contain a soluble inhibitor such as interferon that protected uninfected cells from infection by MHV or vesicular stomatitis virus. The persistent infection was cured if fewer than 100 cells were transferred during subculturing, and such cured cultures were susceptible to reinfection and the reestablishment of persistent infection. Cultures of 17C1-1 cells that had been newly cloned from single cells consisted of a mixture of MHV-resistant and -susceptible cells. 17C1-1/#97 cells, which were cured by subcloning after 97 passages of a persistently infected culture over a 1-year period, contained 5 to 10% of their population as susceptible cells, while 17C1-1/#402 cells, which were cured by subcloning after 402 passages over a 3-year period, had less than 1% susceptible cells. Susceptibility to infection correlated with the expression of MHV receptor glycoprotein (MHVR [Bgp1a]). Fluorescence-activated cell sorter analysis with antibody to MHVR showed that 17C1-1/#97 cells contained a small fraction of MHVR-expressing cells. These MHVR-expressing cells were selectively eliminated within 24 h after challenge with MHV-A59, and pretreatment of 17C1-1/#97 cells with monoclonal antibody CC1, which binds to the N-terminal domain of MHVR, blocked infection. We conclude that the subpopulation of MHVR-expressing cells were infected and killed in acutely or persistently infected cultures, while the subpopulation of MHVR-nonexpressing cells survived and proliferated. The subpopulation of MHVR-negative cells produced a small proportion of progeny cells that expressed MHVR and became infected, thereby maintaining the persistent infection as a steady-state carrier culture. Thus, in 17C1-1 cell cultures, the unstable or epigenetic expression of MHVR permitted the establishment of a persistent, chronic infection.


title: Prediction of repurposed drugs for treating lung injury in COVID-19.

text: Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Inhibition of Angiotensin-converting enzyme 2 (ACE2) caused by spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues, including signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and Chemokine signaling pathways. All these twelve pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares eleven of twelve pathways with COL-3 with common target genes such as RHOA. It also uniquely targets genes related to lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have the potential as repurposed drugs for its treatment.


title: Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study.

text: PURPOSE To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs). METHODS Twelve sites around the world prospectively enrolled 197 patients (mean age 71±11 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category ≥4). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure. RESULTS Technical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization. CONCLUSION Tibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia.


Eye on religion: by the brush and by the sword: Daoist perspectives on the body, illness, and healing.


title: An investigation of incorporation of cellular antigens into vaccinia virus particles.

text: Vaccinia virus (VV) infection produces several types of virus particle called intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). Some cellular antigens are associated with EEV and these vary with the cell type used to grow the virus. To investigate if specific cell antigens are associated with VV particles, and to address the origin of membranes used to envelope IMV and IEV/CEV/EEV, we have studied whether cell antigens and foreign antigens expressed by recombinant VVs are incorporated into VV particles. Membrane proteins that are incorporated into the endoplasmic reticulum (ER), intermediate compartment (IC), cis/medial-Golgi, trans-Golgi network (TGN) or plasma membrane were not detected in purified IMV particles. In contrast, proteins present in the TGN or membrane compartments further downstream in the exocytic pathway co-purify with EEV particles when analysed by immunoblotting. Immunoelectron microscopy found only low levels of these proteins in IEV, CEV/EEV. The incorporation of foreign antigens into VV particles was not affected by loss of individual IEV or EEV-specific proteins or by redirection of B5R to the ER. These data suggest that (i) host cell antigens are excluded from the lipid envelope surrounding the IMV particle and (ii) membranes of the ER, IC and cis/medial-Golgi are not used to wrap IMV particles to form IEV. Lastly, the VV haemagglutinin was absent from one-third of IEV and CEV/EEV particles, whereas other EEV antigens were present in all these virions.


Hard decisions will have to be made: view from intensive care.


title: Dynamic effects of antibody-dependent enhancement on the fitness of viruses.

text: Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which ADE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. We examine the epidemiological impact of ADE on the prevalence and persistence of viral serotypes. Using a dynamical system model of n cocirculating dengue serotypes, we find that ADE may provide a competitive advantage to those serotypes that undergo enhancement compared with those that do not, and that this advantage increases with increasing numbers of cocirculating serotypes. Paradoxically, there are limits to the selective advantage provided by increasing levels of ADE, because greater levels of enhancement induce large amplitude oscillations in incidence of all dengue virus infections, threatening the persistence of both the enhanced and nonenhanced serotypes. Although the models presented here are specifically designed for dengue, our results are applicable to any epidemiological system in which partial immunity increases pathogen replication rates. Our results suggest that enhancement is most advantageous in settings where multiple serotypes circulate and where a large host population is available to support pathogen persistence during the deep troughs of ADE-induced large amplitude oscillations of virus replication.


title: The role of vaccination in the control of sars.

text: We assess pre-outbreak and during-outbreak vaccination as control strategies for SARS epidemics using a mathematical model that includes susceptible, latent (traced and untraced), infectious, isolated and recovered individuals. Scenarios focusing on policies that include contact tracing and levels of self-isolation among untraced infected individuals are explored. Bounds on the proportion of pre-outbreak successfully vaccinated individuals are provided using the the basic reproductive number. Uncertainty and sensitivity analyses on the reproductive number are carried out. The final epidemic size under different vaccination scenarios is computed.


title: Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector.

text: Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization. In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.


title: Inhibition of influenza virus matrix (M1) protein expression and virus replication by U6 promoter-driven and lentivirus-mediated delivery of siRNA.

text: Small interfering RNA (siRNA)-induced RNA degradation has been used recently as an antivirus agent to inhibit specific virus replication. This report shows that 21 nt duplexes of siRNA of the influenza virus M gene can cause specific inhibition of influenza virus matrix (M1) protein expression in transfected 293T cells. Furthermore, it is shown that a lentivirus vector can be used to effectively deliver M gene siRNAs into Madin-Darby canine kidney cells and can cause specific inhibition of M1 protein expression and influenza virus replication. Therefore, lentivirus-mediated delivery of siRNA and gene silencing can be used in studying the specific functions of virus genes in replication and may have a potential therapeutic application.


title: Nonparametric survival analysis of infectious disease data.

text: This paper develops nonparametric methods based on contact intervals for the analysis of infectious disease data. The contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j, where we define infectious contact as a contact sufficient to infect a susceptible individual. The hazard function of the contact interval distribution equals the hazard of infectious contact from i to j, so it provides a summary of the evolution of infectiousness over time. When who-infects-whom is observed, the Nelson-Aalen estimator produces an unbiased estimate of the cumulative hazard function of the contact interval distribution. When who-infects-whom is not observed, we use an EM algorithm to average the Nelson-Aalen estimates from all possible combinations of who-infected-whom consistent with the observed data. This converges to a nonparametric maximum likelihood estimate of the cumulative hazard function that we call the marginal Nelson-Aalen estimate. We study the behavior of these methods in simulations and use them to analyze household surveillance data from the 2009 influenza A(H1N1) pandemic.


title: Deploying aptameric sensing technology for rapid pandemic monitoring.

text: The genome of virulent strains may possess the ability to mutate by means of antigenic shift and/or antigenic drift as well as being resistant to antibiotics with time. The outbreak and spread of these virulent diseases including avian influenza (H1N1), severe acute respiratory syndrome (SARS-Corona virus), cholera (Vibrio cholera), tuberculosis (Mycobacterium tuberculosis), Ebola hemorrhagic fever (Ebola Virus) and AIDS (HIV-1) necessitate urgent attention to develop diagnostic protocols and assays for rapid detection and screening. Rapid and accurate detection of first cases with certainty will contribute significantly in preventing disease transmission and escalation to pandemic levels. As a result, there is a need to develop technologies that can meet the heavy demand of an all-embedded, inexpensive, specific and fast biosensing for the detection and screening of pathogens in active or latent forms to offer quick diagnosis and early treatments in order to avoid disease aggravation and unnecessary late treatment costs. Nucleic acid aptamers are short, single-stranded RNA or DNA sequences that can selectively bind to specific cellular and biomolecular targets. Aptamers, as new-age bioaffinity probes, have the necessary biophysical characteristics for improved pathogen detection. This article seeks to review global pandemic situations in relation to advances in pathogen detection systems. It particularly discusses aptameric biosensing and establishes application opportunities for effective pandemic monitoring. Insights into the application of continuous polymeric supports as the synthetic base for aptamer coupling to provide the needed convective mass transport for rapid screening is also presented.


title: GyDB mobilomics: LTR retroelements and integrase-related transposons of the pea aphid Acyrthosiphon pisum genome.

text: The Gypsy Database concerning Mobile Genetic Elements (release 2.0) is a wiki-style project devoted to the phylogenetic classification of LTR retroelements and their viral and host gene relatives characterized from distinct organisms. Furthermore, GyDB 2.0 is concerned with studying mobile elements within genomes. Therefore, an in-progress repository was created for databases with annotations of mobile genetic elements from particular genomes. This repository is called Mobilomics and the first uploaded database contains 549 LTR retroelements and related transposases which have been annotated from the genome of the Pea aphid Acyrthosiphon pisum. Mobilomics is accessible from the GyDB 2.0 project using the URL: http://gydb.org/index.php/Mobilomics.


title: Pulse oximetry and high-dose vasopressors: a comparison between forehead reflectance and finger transmission sensors.

text: PURPOSE Pulse oximetry (SpO(2)) measured at finger site via transmission mode may fail in situations of hypoperfusion. Forehead sensors using reflectance technology might be useful in these circumstances. We hypothesized that reflectance SpO(2) would be more accurate than finger SpO(2) in patients with severe shock. METHODS A prospective observational study was conducted in an intensive care unit of a university hospital of patients in shock who were treated with high norepinephrine and/or epinephrine doses (≥0.1 μg kg(-1) min(-1)). When blood gas determinations were requested, forehead SpO(2) and finger SpO(2) values were simultaneous recorded. Agreement between SpO(2) measurements with arterial saturation (SaO(2)), obtained by blood analysis with a co-oximeter, was assessed using the Bland-Altman method. The number of outliers, defined by the formula SaO(2) - SpO(2) > ±3 %, indicated the proportion of measurements considered to be clinically unacceptable. RESULTS Thirty-two patients were enrolled in the study. With the forehead sensor no reading failure occurred, and 140 paired data sets (forehead SpO(2) vs. SaO(2)) were obtained. Bias and precision were +1.0 and +2.5 %, respectively, and the limits of agreement ranged from -4.0 to 6.0 %. The finger sensor failed to give a value in four cases, thus providing 136 paired data sets (finger SpO(2) vs. SaO(2)) for analysis. Bias and precision were +1.4 and +4.8 %, respectively, and the limits of agreement ranged from -8.0 to 10.9 %. There were 21 (15 %) outliers for the forehead sensor and 43 (32 %) for the finger sensor (P < 0.001). CONCLUSIONS Forehead SpO(2) measurements were more accurate than finger SpO(2) when compared with SaO(2) in critically ill patients requiring high-dose vasopressor therapy and should therefore be the preferred method considered.


title: Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation.

text: In April 2012, an outbreak of acute respiratory illness occurred in a public hospital in Zarqa city, in Jordan; 8 health care workers were among the 11 people affected, 1 of who later died. The cause of the outbreak was unknown at the time and an epidemiological investigation including laboratory testing carried out immediately afterthe outbreak was inconclusive. Following the discovery of novel coronavirus infection (nCoV) in the Arabian peninsula in September 2012, stored respiratory and serum samples of patients from this outbreak were retested and the diagnosis of nCoV was confirmed in 2 deceased patients. This paper describes the epidemiological findings of retrospective investigation carried out in November 2012 and highlights the likelihood of nosocomial transmission of nCoV infection in a health-care setting. A total of 2 laboratory-confirmed and 11 probable cases were identified from this outbreak of whom 10 were HCWs and 2 were family members of cases.


title: Epitope mapping of the major capsid protein of type 2 porcine circovirus (PCV2) by using chimeric PCV1 and PCV2.

text: Type 2 porcine circovirus (PCV2) is associated with postweaning multisystemic wasting syndrome in pigs, whereas the genetically related type 1 PCV (PCV1) is nonpathogenic. In this study, seven monoclonal antibodies (MAbs) against PCV2-ORF2 capsid protein were generated, biologically characterized, and subsequently used to map the antigenic sites of PCV2 capsid protein by using infectious PCV DNA clones containing PCV1/PCV2-ORF2 chimeras. The PCV1/PCV2-ORF2 chimeras were constructed by serial deletions of PCV2-ORF2 and replacement with the corresponding sequences of the PCV1-ORF2. The reactivities of chimeric PCV1/PCV2 clones in transfected PK-15 cells with the seven MAbs were detected by an immunofluorescence assay (IFA). The chimera (r140) with a deletion of 47 amino acids at the N terminus of PCV2-ORF2 reacted strongly to all seven MAbs. Expanding the deletion of PCV2-ORF2 from residues 47 to 57 (r175) abolished the recognition of MAb 3B7, 3C11, 4A10, 6H2, or 8F6 to the chimera. Further deletion of PCV2-ORF2 to 62 residues disrupted the binding of this chimera to all seven MAbs. IFA reactivities with all MAbs were absent when residues 165 to 233 at the C terminus of PCV2-ORF2 was replaced with that of PCV1-ORF2. Extending the sequence of PCV2-ORF2 from residues 165 (r464) to 185 (r526), 200 (r588), or 224 (r652) restored the ability of the three chimeras to react with MAbs 3C11, 6H2, 9H7, and 12G3 but not with 8F6, 3B7, or 4A10. When the four amino acids at the C terminus of r588 were replaced with that of PCV2-ORF2, the resulting chimera (r588F) reacted with all seven MAbs. The results from this study suggest that these seven MAbs recognized at least five different but overlapping conformational epitopes within residues 47 to 63 and 165 to 200 and the last four amino acids at the C terminus of the PCV2 capsid protein.


title: Use of synthetic antigens improves detection by enzyme-linked immunosorbent assay of antibodies against abortigenic Chlamydia psittaci in ruminants.

text: Synthetic peptide antigens were prepared for use in enzyme-linked immunosorbent assays (ELISAs) to detect serum antibodies against abortigenic strains of Chlamydia psittaci in livestock. Peptide antigens were identified with C. psittaci B577-immune sera by solid-phase scanning of overlapping octapeptides of variable domains (VDs) of the major outer membrane protein of C. psittaci serovar 1 (omp1 type C. psittaci B577). Two VD 4 regions and one VD 2 region were strongly reactive with all C. psittaci B577 antisera. Peptides encompassing these regions were synthesized with biotin and a serine-glycine-serine-glycine spacer at the N terminus and were attached to streptavidin-coated microtiter plates. In direct ELISAs with these plates, the synthetic peptides reacted with C. psittaci B577 antisera, but not with sera from specific-pathogen-free animals. Serum specimens from 40 sheep and 40 cattle, obtained from herds with abortion problems, were screened for antibodies by these C. psittaci B577 peptide ELISAs and an ELISA with recombinant, genus-specific Chlamydia lipopolysaccharide (LPS) antigen. Results from these newly developed ELISAs were compared to those from the reference C. psittaci B577 elementary body (EB) ELISA and the Chlamydia complement fixation test (CFT). The C. psittaci B577 peptide ELISAs, the LPS ELISA, and the EB ELISA correctly identified the presence or absence of antibodies against chlamydiae in all sheep and bovine sera. The Chlamydia CFT, which is the most widely accepted serodiagnostic method for chlamydial infections in animals, correctly identified the presence or absence of antibodies against chlamydiae in only 78 and 4.9% of sheep and bovine sera, respectively. These results suggest that the C. psittaci B577-peptide and Chlamydia LPS ELISAs are superior for the serodiagnosis of ruminant infections with abortigenic chlamydiae, since they are more sensitive than the CFT, they are easy to standardize, and they use readily available synthetic antigens instead of organism-derived CFT antigen.


Back to the future: rebuilding public health infrastructure.


title: Surge capacity and casualization: Human resource issues in the post-SARS health system.

text: In Ontario, the unpredictable funding climate of the 1990s led health care organizations to look for ways to reduce costs. Adopting a just-in-time staffing policy, they employed fewer full-time workers, scheduled part-time workers to work regular shifts, took on more casual staff, and became increasingly reliant on agency nurses and overtime to cover shifts. These policies resulted in higher costs and reduced surge capacity, and placed the health of nurses and patients in jeopardy. Fewer staff meant more overtime. Stress-related absenteeism increased. Some nurses reacted to casualization by working for multiple employers. During the SARS (severe acute respiratory syndrome) epidemic in Toronto, nursing resources were stretched to their limits. An exploratory investigation, based on relevant literature and interviews with 13 nurse administrators who held key positions during the epidemic, confirmed the lack of spare capacity in the health care system and indicated that community and long-term care sectors had less capacity than acute care. Low surge capacity in these sectors increased the vulnerability of the entire health care system. Capacity issues should be addressed as part of a larger human resources initiative to create a more flexible workforce. Since SARS, a number of government and organizational initiatives have been developed to increase nursing capacity.


title: Two types of bacteria adherent to bovine respiratory tract ciliated epithelium.

text: Two hundred sixty tracheas were obtained from a Philadelphia abattoir under permit from the Department of Agriculture; the tracheas were excised from predominantly Holstein calves of both sexes that weighed approximately 250 kg. Tracheas were transported in normal saline to the laboratory at Thomas Jefferson University, Philadelphia, Pennsylvania. Evidence of bacteria adherent to the tracheal epithelium was found in specimens from 20/24 of these tracheas. The epithelium from each of five tracheas was placed in glutaraldehyde fixative for transmission electron microscopic examination. Epithelium from each of 12 other tracheas was placed in formaldehyde fixative for light microscopic examination. Microscopically, 13 of these 17 bovine tracheal epithelia were observed to contain bacteria located longitudinally parallel to and between cilia and microvilli of ciliated cells. Preparations of ciliary axonemes isolated from the epithelium of seven additional bovine tracheas also contained these bacteria in sections viewed by a transmission electron microscope. These bacteria had two different ultrastructural morphologies: filamentous with a trilaminar-structured cell wall and short with a thick, homogeneously stained cell wall beneath a regularly arrayed surface layer. The short bacillus had surface carbohydrates, including mannose, galactose, and N-acetylgalactosamine, identified by lectin binding. The filamentous bacillus was apparently externally deficient in these carbohydrates. Immunogold staining revealed that the filamentous bacillus was antigenically related to cilia-associated respiratory (CAR) bacillus, which has been identified in rabbit and rodent species. Significantly decreased numbers of cilia were obtained from tracheal epithelium heavily colonized by the filamentous bacilli, suggesting a pathologic change in ciliated cells.


title: Epidemiology of SARS in the 2003 Hong Kong epidemic.

text: 1. The temporal and spatial evolution of the SARS epidemic in Hong Kong is described. 2. Estimates of key epidemiological distributions and their stability over the course of the epidemic are derived. 3. The characteristics of those who contracted the disease are determined including factors associated with the likelihood of mortality as a result of SARS coronavirus infection.


title: Evolution of bombesin conjugates for targeted PET imaging of tumors.

text: Bombesin receptors are under intense investigation as molecular targets since they are overexpressed in several prevalent solid tumors. We rationally designed and synthesized a series of modified bombesin (BN) peptide analogs to study the influence of charge and spacers at the N-terminus, as well as amino acid substitutions, on both receptor binding affinity and pharmacokinetics. This enabled development of a novel (64/67)Cu-labeled BN peptide for PET imaging and targeted radiotherapy of BN receptor-positive tumors. Our results show that N-terminally positively charged peptide ligands had significantly higher affinity to human gastrin releasing peptide receptor (GRPr) than negatively charged or uncharged ligands (IC(50): 3.2±0.5 vs 26.3±3.5 vs 41.5±2.5 nM). The replacement of Nle(14) by Met, and deletion of D-Tyr(6), further resulted in 8-fold higher affinity. Contrary to significant changes to human GRPr binding, modifications at the N-terminal and at the 6(th), 11(th), and 14(th) position of BN induced only slight influences on affinity to mouse GRPr. [Cu(II)]-CPTA-[βAla(11)] BN(7-14) ([Cu(II)]-BZH7) showed the highest internalization rate into PC-3 cells with relatively slow efflux because of its subnanomolar affinity to GRPr. Interestingly, [(64/67)Cu]-BZH7 also displayed similar affinities to the other 2 human BN receptor subtypes. In vivo studies showed that [(64/67)Cu]-BZH7 had a high accumulation in PC-3 xenografts and allowed for clear-cut visualization of the tumor in PET imaging. In addition, a CPTA-glycine derivative, forming a hippurane-type spacer, enhanced kidney clearance of the radiotracer. These data indicate that the species variation of BN receptor plays an important role in screening radiolabeled BN. As well, the positive charge from the metallated complex at the N-terminal significantly increases affinity to human GRPr. Application of these observations enabled the novel ligand [(64/67)Cu]-BZH7 to clearly visualize PC-3 tumors in vivo. This study provides a strong starting point for optimizing radiopeptides for targeting carcinomas that express any of the BN receptor subtypes.


title: Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience.

text: PURPOSE To report the initial experience regarding thin-section computed tomographic (CT) findings in patients with severe acute respiratory syndrome (SARS) who improved clinically after treatment. MATERIALS AND METHODS Twenty-four patients (10 men, 14 women; mean age, 39 years; age range, 23-70 years) with confirmed SARS underwent follow-up thin-section CT of the thorax. The scans were obtained on average 36.5 days after hospital admission and were analyzed for parenchymal abnormality (ground-glass opacification, consolidation, or interstitial thickening) and evidence of fibrosis (parenchymal band, traction bronchiectasis, irregular interfaces). Patients were assigned to group 1 (with CT evidence of fibrosis) and group 2 (without CT evidence of fibrosis) for analysis. Patient demographics, length of hospital stay, rate of intensive care unit admission, peak lactate dehydrogenase level, pulsed intravenous methylprednisolone therapy, and peak opacification on chest radiographs were compared between the two groups. RESULTS Parenchymal abnormality was found in 96% (23 of 24) of patients and ranged from residual ground-glass opacification and interstitial thickening in group 2 (nine of 24, 38%) to fibrosis in group 1 (15 of 24, 62%). Patients in group 1 were older (mean age, 45 vs 30.3 years), had a higher rate of intensive care unit admission (27% [four of 15] vs 11% [one of nine]), more requirement for pulsed intravenous methylprednisolone (87%, [13 of 15] vs 67% [six of nine]), higher peak lactate dehydrogenase level (438.9 vs 355.6 U/L), and higher peak opacification on chest radiographs (estimated area, 14% vs 11%) than patients in group 2. CONCLUSION Pulmonary fibrosis may develop early in patients with SARS who have been discharged after treatment. Patients who are older and have more severe disease during treatment are more likely to develop thin-section CT findings of fibrosis.


title: Response to a standard behavioral weight loss intervention by age of onset of obesity.

text: BACKGROUND The purpose of this study was to examine weight loss, physical activity, fitness and diet changes in response to a standard behavioral weight loss intervention in adults with self-reported juvenile onset (n = 61) or adult onset (n = 116) obesity. METHODS Participants (n = 177; 43.0 ± 8.6 years; body mass index [BMI] = 33.0 ± 3.4 kg m-2) engaged in an 18-month standard behavioral weight loss intervention. Participants were randomized into three different intervention groups as part of the larger parent trial. BMI, physical activity, fitness and diet were assessed at baseline, 6, 12 and 18 months. Separate adjusted mixed models were constructed using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS There was significant weight loss, increased physical activity, improved fitness and reduced caloric intake over time (p < 0.001). There were no significant differences in these outcome variables by obesity onset group. However, there was a significant group by time interaction for fitness (p = 0.001), with the adult onset making significantly greater gains in fitness from baseline to 6 months (p < 0.001); however, this difference was no longer present at 12 or 18 months. CONCLUSIONS With the exception of fitness at 6 months, weight loss, physical activity and diet did not differ between juvenile onset and adult onset participants, suggesting that those with juvenile onset obesity are equally responsive to a standard behavioral weight loss intervention in adulthood.


title: Coupling molecular beacons to barcoded metal nanowires for multiplexed, sealed chamber DNA bioassays.

text: We have combined molecular beacon (MB) probes with barcoded metal nanowires to enable no-wash, sealed chamber, multiplexed detection of nucleic acids. Probe design and experimental parameters important in nanowire-based MB assays are discussed. Loop regions of 24 bases and 5 base pair stem regions in the beacon probes gave optimal performance. Our results suggest that thermodynamic predictions for secondary structure stability of solution-phase MB can guide probe design for nanowire-based assays. Dengue virus-specific probes with predicted solution-phase DeltaG of folding in 500 mM buffered NaCl of approximately -4 kcal/mol performed better than those with DeltaG > -2 or < -6 kcal/mol. Buffered 300-500 mM NaCl was selected after comparison of several buffers previously reported for similar types of assays, and 200-500 mM NaCl was found to be the optimal ionic strength for the hybridization temperatures (25 and 50 degrees C) and probe designs used here. Target binding to the surface as a function of solution concentration fit a Sips isotherm with Kd = 1.7 +/- 0.3 nM. The detection limit was approximately 100 pM, limited by incomplete quenching. Single base mismatches could be discriminated from fully complementary targets. Oligonucleotide target sequences specific for human immunodeficiency, hepatitis C, and severe acute respiratory viruses were assayed simultaneously in a no-wash, sealed chamber, multiplexed experiment in which each of three probe sequences was attached to a different pattern of encoded nanowires. Finally, we demonstrated that probe-coated nanowires retain their selectivity and sensitivity in a triplexed assay after storage for over 3 months.


title: Optimization of a DNA vaccine against SARS.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) first appeared in Southern China in November 2002, and then quickly spread to 33 countries on five continents along international air travel routes. Although the SARS epidemic has been contained, there is a clear need for a safe and effective vaccine should an outbreak of a SARS-CoV infection reappear in human population. In this study, we tested four DNA-vaccine constructs: (1) pLL70, containing cDNA for the SARS-CoV spike (S) gene; (2) pcDNA-SS, containing codon-optimized S gene for SARS-CoV S protein (residues 12-1255) fused with a leader sequence derived from the human CD5 gene; (3) pcDNA-St, containing the gene encoding the N-portion of the codon-optimized S gene (residues 12-532) with the CD5 leader sequence; (4) pcDNA-St-VP22C, containing the gene encoding the N-portion of the codon-optimized S protein with the CD5 leader sequence fused with the C-terminal 138 amino acids of the bovine herpesvirus-1 (BHV-1) major tegument protein VP22. Each of these plasmids was intradermally administered to C57BL/6 mice in three separate immunizations. Analysis of humoral and cellular immune responses in immunized mice demonstrated that pcDNA-SS and pcDNA-St-VP22C are the most immunogenic SARS vaccine candidates.


title: Rat glial C6 cells are defective in murine coronavirus internalization.

text: Rat C6 glial cells were resistant to infection by several strains of murine coronaviruses. The restriction was not at the adsorption stage, since virus adsorbed to the C6 cells in a similar manner to mouse L cells which supported a lytic infection. The virus could not be internalized by the C6 cells. However, if the virus was introduced into the C6 cells by polyethylene glycol fusion, viral replication occurred and progeny virions were released from the infected cells. These studies indicated that the C6 cells were restrictive to coronavirus replication by preventing the early penetration stage of the viral replicative cycle.


title: Mechanisms of type-I- and type-II-interferon-mediated signalling.

text: Interferons are cytokines that have antiviral, antiproliferative and immunomodulatory effects. Because of these important properties, in the past two decades, major research efforts have been undertaken to understand the signalling mechanisms through which these cytokines induce their effects. Since the original discovery of the classical JAK (Janus activated kinase)-STAT (signal transducer and activator of transcription) pathway of signalling, it has become clear that the coordination and cooperation of multiple distinct signalling cascades - including the mitogen-activated protein kinase p38 cascade and the phosphatidylinositol 3-kinase cascade - are required for the generation of responses to interferons. It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance our current thinking about how interferons work.


title: C-Reactive Protein in Orthopaedic Surgery.

text: C-reactive protein (CRP) is a common laboratory infection marker in blood-serum of patients. In all diverse medical departments CRP is often used, and also in orthopaedics CRP is proved to be very helpful in diagnosis and monitor of infections. CRP in most fields is superior to conventional and newer infection parameter and is a basic parameter for inflammation. Especially for detection of an early postoperative infection CRP can be very helpful as an objective parameter easy to obtain. In uneventful operative treatment a similar evolution in CRP concentrations was found: the peak level occurred on the second or third postoperative day and reflected the extent of surgical trauma. A second rise of CRP in the postoperative course indicates a complication. Highest levels are reached in bacterial infection after the forth postoperative day with a cut-off level about 10 mg/dl. CRP can also be used as a preoperative marker for risk stratification and newer times CRP is reported as an independent fracture-risk-factor. In general CRP is the basic inflammatory parameter in orthopaedic surgery and is more significant and common than WBC or ESR. But CRP is only a laboratory parameter and must always be correlated with clinical signs of infection.


title: Reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies-Depression (CES-D) Scale.

text: INTRODUCTION The aim of the current study was to assess the reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies- Depression Scale (CES-D). METHODS 40 depressed patients 29.65 +/- 9.38 years old, and 120 normal controls 27.23 +/- 10.62 years old entered the study. In 20 of them (12 patients and 8 controls) the instrument was re-applied 1-2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbach's alpha (alpha) RESULTS Both Sensitivity and specificity exceed 90.00 at 23/24, Chronbach's alpha for the total scale was equal to 0.95. Factor analysis revealed three factors (positive affect, irritability and interpersonal relationships, depressed affect and somatic complains). The test-retest reliability was satisfactory (Pearson's R between 0.45 and 0.95 for individual items and 0.71 for total score). CONCLUSION The Greek translation of the CES-D scale is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature. However one should always have in mind the limitations inherent in the use of self-report scales.


title: Coronavirus JHM: tryptic peptide fingerprinting of virion proteins and intracellular polypeptides.

text: The virion proteins and intracellular polypeptides of the murine coronavirus MHV-JHM have been analysed by two-dimensional fingerprinting of their [35S]methionine-containing tryptic peptides. The analysis shows that the virion proteins gp98, gp65, pp60 and p23 are distinct. Virion protein gp25 has the same polypeptide component as p23, and virion protein gp170 has a polypeptide component related to gp98. The six virus polypeptides synthesized in infected cells, 150K, 65K, 60K, 30K, 23K and 14K are also distinct. The 170K and 98K species, which are produced by processing, are related to 150K. The 25K species is a processed form of 23K. The identity of corresponding species in the cell and in the virion has been shown and a model describing the genesis of coronavirus JHM proteins can now be proposed.


title: Epidemiological and experimental evidence for immunodeficiency affecting avian infectious bronchitis.

text: We evaluated the effects of viral immunodeficiency on the outcome of infectious bronchitis virus (IBV) infection in chickens as a hypothetical cause for failure of adequate protection in vaccinated chickens. Initially, we investigated IBV isolations from cases of respiratory disease in association with the presence of thymic and/or bursal atrophy in 322 submissions during 1997 to 2002. Arkansas (Ark)-type IBV was most frequently isolated in spite of extensive ArkDPI vaccination in the broiler industry. The number of IBV isolations was consistently higher in broilers aged 27 to 43 days, coinciding with lymphocytic depletion of the bursa and/or thymus, providing circumstantial evidence that immunodeficiency and IBV incidence may be linked. S1 gene sequence analyses, antigenic characterizations, and challenge of susceptible chickens demonstrated that the field IBV isolates tested were closely related to vaccine strains and had low pathogenicity for chickens. We experimentally evaluated the effects of immunodeficiency caused by co-infection with chicken anaemia virus and infectious bursal disease virus on the outcome of IBV infection. Clinical signs and histological lesions were more persistent in immunodeficient chickens. Local specific IgA production was delayed and lower levels were achieved in immunodeficient chickens. At the same time, IBV RNA concentrations in tracheas and lachrymal fluids were higher and more persistent in immunodeficient chickens. Collectively, these results indicate that viral immunodeficiency most probably plays a relevant role in the epidemiology and outcome of IBV infection.


title: Selection in persistently infected murine cells of an MHV-A59 variant with extended host range.

text: Murine coronavirus MHV-A59 normally infects only murine cells in vitro and causes transmissible infection only in mice. In the 17 C1 1 line of murine cells, the receptor for MHV-A59 is MHVR, a biliary glycoprotein in the carcinoembryonic antigen (CEA) family of glycoproteins. We found that virus released from the 600th passage of 17 C1 1 cells persistently infected with MHV-A59 (MHV/pi600) replicated in hamster (BHK-21) cells. The virus was passaged and plaque-purified in BHK-21 cells, yielding the MHV/BHK strain. Because murine cells persistently infected with MHV-A59 express a markedly reduced level of MHVR (Sawicki, et al., 1995), we tested whether virus with altered receptor interactions was selected in the persistently infected culture. Infection of 17 C1 1 cells by MHV-A59 can be blocked by treating the cells with anti-MHVR MAb-CC1, while infection by MHV/BHK was only partially blocked by MAb-CC1. MHV/BHK virus was also more resistant than wild-type MHV-A59 to neutralization by purified, recombinant, soluble MHVR glycoprotein (sMHVR). Cells in the persistently infected culture may also express reduced levels of and have altered interactions with some of the Bgp-related glycoproteins that can serve as alternative receptors for MHV-A59. Unlike the parental MHV-A59 which only infects murine cells, MHV/BHK virus was able to infect cell lines derived from mice, hamsters, rats, cats, cows, monkeys and humans. However, MHV/BHK was not able to infect all mammalian species, because a pig (ST) cell line and a dog cell line (MDCK I) were not susceptible to infection. MHV/pi600 and MHV/BHK replicated in murine cells more slowly than MHV-A59 and formed smaller plaques. Thus, in the persistently infected murine cells which expressed a markedly reduced level of MHVR, virus variants were selected that have altered interactions with MHVR and an extended host range. In vivo, in mice infected with coronavirus, virus variants with altered receptor recognition and extended host range might be selected in tissues that have low levels of receptors. Depending upon the tissue in which such a virus variant was selected, it might be shed from the infected animal or eaten by a predator, thus presenting a possible means for initiating the transition of a variant virus into a new host as a model for an emerging virus disease.


Harnessing new science is vital for biodefense and global health.


title: Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure.

text: Inhaled nitric oxide (INO) is a colorless, odorless gas that is also a potent pulmonary vasodilator. When given via the inhaled route it is a selective pulmonary vasodilator. INO is approved by the United States Food and Drug Administration (FDA) for the treatment of term and near-term neonates with hypoxemic respiratory failure associated with clinical or echocardiographic evidence of pulmonary arterial hypertension. A systematic review of the literature was conducted with the intention of making recommendations related to the clinical use of INO for its FDA-approved indication. Specifically, we wrote these evidence-based clinical practice guidelines to address the following questions: (1) What is the evidence for labeled use? (2) What are the specific indications for INO for neonates with acute hypoxemic respiratory failure? (3) Does the use of INO impact oxygenation, mortality, or utilization of extracorporeal membrane oxygenation (ECMO)? (4) Does INO affect long-term outcomes? (5) Is INO cost-effective therapy? (6) How is the appropriate dosing regimen and dose response to INO established? (7) How is the dose of INO titrated and weaned? (8) Which INO delivery system should be used? (9) How should INO be implemented with different respiratory support devices? (10) What adverse effects of INO should be monitored, and at what frequency? (11) What physiologic parameters should be monitored during INO? (12) Is scavenging of gases necessary to protect the caregivers? Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring system, 22 recommendations are developed for the use of INO in newborns.


COVID-19: the new challenge for rheumatologists. First update.


title: Familial Mediterranean Fever.

text: Familial Mediterranean Fever is a genetic disorder frequently diagnosed among the Arabs. It is also prevalent among Jews, Armenians and Turks. The clinical picture consists of febrile and painful attacks that differ in quality across patients and even within the same patient. There may be accompanying joint pain, chest pain, skin manifestations and other findings, and amyloidosis may occur in some patients as a complication. The primary treatment is Colchicine, which decreases the frequency of the attacks and prevents the occurrence of amyloidosis. The gene responsible for Familial Mediterranean Fever, MEFV, has been mapped and cloned and mutations were identified within its coding sequence. It encodes a protein that is expected to be a down regulator of inflammation. The spectrum of mutations in the Arabic population is partially studied. There are still several issues to be solved before we fully understand the disorder, and to enable us to confront it and decrease the morbidity and mortality inflicted by it.


title: Clinical use of cerebral oximetry in extremely preterm infants is feasible.

text: INTRODUCTION The research programme Safeguarding the Brains of our smallest Children (SafeBoosC) aims to test the benefits and harms of cerebral near-infrared spectroscopy (NIRS) oximetry in infants born before 28 weeks of gestation. In a phase II trial, infants will be randomised to visible cerebral NIRS oximetry with pre-specified treatment guidelines compared to standard care with blinded NIRS-monitoring. The primary outcome is duration multiplied with the extent outside the normal range of regional tissue oxygen saturation of haemoglobin (rStO2) of 55 to 85% in percentage hours (burden). This study was a pilot of the Visible -Oximetry Group. MATERIAL AND METHODS This was an observational study including ten infants. RESULTS The median gestational age was 26 weeks+three days, and the median start-up time was 133 minutes after delivery. The median recording time was 69.7 hours, mean rStO2 was 64.2±4.5%, median burden of hyper- and hypoxia was 30.3% hours (range 2.8-112.3). Clinical staff responded to an out of range value 29 times--only once to values above 85%. In comparison, there were 83 periods of more than ten minutes with an rStO2 below 55% and four episodes with an rStO2 above 85%. These periods accounted for 72% of the total hypoxia burden. A total of 18 of the 29 interventions were adjustments of FiO2 which in 13 of the 18 times resulted in an out-of-range SpO2. Two infants suffered second-degree burns from the sensor. Five infants died. In all cases, this was unrelated to NIRS monitoring and treatment. CONCLUSION The intervention of early cerebral NIRS monitoring proved feasible, but prolonged periods of hypoxia went untreated. Thus, a revision of the treatment guideline and an alarm system is required. FUNDING The Elsass Foundation funded the present study. TRIAL REGISTRATION Clinicaltrials.gov: NCT01530360.


title: Strategies for improving influenza immunization rates among hard-to-reach populations.

text: Whereas considerable attention has been devoted to achieving high levels of influenza immunization, the importance of this issue is magnified by concern over pandemic influenza. Most recommendations for vaccine administration address high risk groups such as the elderly and those with chronic diseases, but coverage for hard-to-reach (HTR) populations has had less attention. HTR populations include minorities but also include other primarily urban groups such as undocumented immigrants, substance users, the homeless, and homebound elderly. Obstacles to the provision of immunization to HTR populations are present at the patient, provider, and structural levels. Strategies at the individual level for increasing immunization coverage include community-based educational campaigns to improve attitudes and increase motivation for receiving vaccine; at the provider level, education of providers to encourage immunizations, improving patient-provider interactions, broadening the provider base to include additional nurses and pharmacists, and adoption of standing orders for immunization administration; and at the structural level, promoting wider availability of and access to vaccine. The planning process for an influenza pandemic should include community engagement and extension of strategies beyond traditional providers to involve community-based organizations addressing HTR populations.


title: Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis.

text: BACKGROUND Chemokine-like factor 1 (CKLF1) was recently identified as a novel cytokine. The full-length CKLF1 cDNA contains 530 bp encoding 99 amino acid residues with a CC motif similar to that of other CC family chemokines. Recombinant CKLF1 exhibits chemotactic activity on leucocytes and stimulates proliferation of murine skeletal muscle cells. We questioned whether CKLF1 could be involved in the pathogenesis of inflammation and proliferation in the lung. Therefore we used efficient in vivo gene delivery method to investigate the biological effect of CKLF1 in the murine lung. METHODS CKLF1-expressing plasmid, pCDI-CKLF1, was constructed and injected into the skeletal muscles followed by electroporation. Lung tissues were obtained at the end of week 1, 2, 3 and 4 respectively after injection. The pathological changes in the lungs were observed by light microscope. RESULTS A single intramuscular injection of CKLF1 plasmid DNA into BALB/c mice caused dramatic pathological changes in the lungs of treated mice. These changes included peribronchial leukocyte infiltration, epithelial shedding, collagen deposition, proliferation of bronchial smooth muscle cells and fibrosis of the lung. CONCLUSIONS The sustained morphological abnormalities of the bronchial and bronchiolar wall, the acute pneumonitis and interstitial pulmonary fibrosis induced by CKLF1 were similar to phenomena observed in chronic persistent asthma, acute respiratory distress syndrome and severe acute respiratory syndrome. These data suggest that CKLF1 may play an important role in the pathogenesis of these important diseases and the study also implies that gene electro-transfer in vivo could serve as a valuable approach for evaluating the function of a novel gene in animals.


title: Application of nanoscale silver-doped titanium dioxide as photocatalyst for indoor airborne bacteria control: a feasibility study in medical nursing institutions.

text: The deterioration of indoor air quality because of airborne bacterial consortia is a widespread environmental problem. The main objective of this study is to evaluate the feasibility of applying nanoscale silver-doped titanium dioxide (TiO2) photocatalysis (nano-Ag/TiO2) particles as a photocatalyst to enhance the disinfecting capability of bacterial restraining equipment in a medical nursing institution. A full-scale, on-site study was initiated to test the effectiveness of adding the photocatalyst to various air quality control equipments; that is, fixed full-covering type (FF type), underneath swinging type (US type), and lateral swinging type (LS type). Results from this study indicate that the FF type has the best bacterial restraining rate (81%) as compared with the LS type (66%) and the US type (61%). Similar results are obtained at different heights (90 and 180 cm) of the nursing institutions, revealing that freshly disinfected air is provided regardless of location as long as the air quality control equipment is in operation. The proposed equipment can disinfect air to effectively restrain bacteria as demonstrated on-site in medical nursing institutions; the results will also be for designing integrated, commercialized, large-scale applications in the future.


title: Effects of IgY against Candida albicans and Candida spp. Adherence and Biofilm Formation.

text: The fungal pathogen Candida albicans is an opportunistic fungal pathogen that causes oral and vaginal mucosal infections as well as systemic disease. The ability of C. albicans to adhere to host surfaces is positively correlated with its pathogenicity. We prepared a polyclonal anti-Candida albicans antibody in chicken egg yolk (anti-C. albicans IgY) and investigated its in vitro effectiveness in preventing C. albicans adherence and biofilm formation. Anti-C. albicans IgY significantly reduced the adherence of C. albicans SC5314 to human oral epithelial cells in a dose-dependent manner. The same effect was also observed in other Candida spp. including C. albicans serotype A and B. Further, the IgY inhibited biofilm formation of C. albicans in medium without serum, but the inhibition was slightly restored in medium conditioned with 10% serum. The data indicate that anti-C. albicans IgY cross-reacted with various Candida spp. and may have a protective effect against oral candidiasis and reduce the dissemination of Candida spp. This effect may be due to the blocking of the binding of Candida spp. to the host cells. However, the blocking did not play a role when Candida formed a germ tube in the presence of serum. Therefore, anti-C. albicans IgY may be considered as a prophylactic immunotherapy or possibly an adjunctive antifungal therapy under limited conditions.


title: Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein.

text: The spike glycoprotein (S) of coronavirus, the major target for virus-neutralizing antibodies, is assumed to mediate the attachment of virions to the host cell. A 26-kilodalton fragment proteolytically cleaved from transmissible gastroenteritis virus (TGEV) S protein was previously shown to bear two adjacent antigenic sites, A and B, both defined by high-titer neutralizing antibodies. Recombinant baculoviruses expressing C-terminal truncations of the 26-kilodalton region were used to localize functionally important determinants in the S protein primary structure. Two overlapping 223- and 150-amino-acid-long products with serine 506 as a common N terminus expressed all of the site A and B epitopes and induced virus-binding antibodies. Coexpression of one of these truncated protein S derivatives with aminopeptidase N (APN), a cell surface molecule acting as a receptor for TGEV, led to the formation of a complex which could be immunoprecipitated by anti-S antibodies. These data provide evidence that major neutralization-mediating and receptor-binding determinants reside together within a domain of the S protein which behaves like an independent module. In spite of their ability to prevent S-APN interaction, the neutralizing antibodies appeared to recognize a preformed complex, thus indicating that antibody- and receptor-binding determinants should be essentially distinct. Together these findings bring new insight into the molecular mechanism of TGEV neutralization.


title: Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.

text: Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.


title: Canine coronavirus infections in Japan: virological and epidemiological aspects.

text: Ten strains, eight field and two reference laboratory strains, of canine coronavirus (CCV) were comparatively examined with respect to antigenic relationships and pathogenic potential in dogs. With monoclonal antibodies and hyperimmune antisera to feline coronavirus and CCV, respectively, varying degrees of antigenic diversities were found among the strains by neutralization and immunofluorescence assays, but it was felt that they belong to one serotype. Specific-pathogen-free puppies experimentally inoculated with some CCV strains manifested clinical symptoms, but there was a difference in their virulence. In order to elucidate the prevalence of CCV infections in dogs in Japan, we tested for neutralizing antibodies to CCV in 467 field dogs, and found a prevalence of 44.1%. Moreover, by using nested reverse transcriptase-polymerase chain reaction on rectal swabs of 100 diarrheic dogs recently presented in veterinary clinics, evidence of CCV in 16% of these specimens was found. The results suggested that CCV infection is more widespread than expected in dogs, and that CCV is a significant etiologic factor in canine diarrhea also in Japan.


Accurate clinical prediction of severe acute respiratory syndrome: are we there yet?


title: Molecular and phylogenetic analysis of a novel turkey-origin picobirnavirus.

text: A previous metagenomic analysis of the turkey gut RNA virus community identified novel enteric viruses that may play roles in poultry enteric diseases or in performance problems noted in the field. As part of the molecular characterization of these novel enteric viruses, a reverse transcriptase-PCR diagnostic assay was developed, targeting a novel turkey-origin picobirnavirus (PBV) initially identified in a pooled intestinal sample from turkey poults in North Carolina. Little detailed molecular information exists regarding the family Picobirnaviridae, particularly for the PBVs that have been described in avian species. This diagnostic assay targets the turkey PBV RNA-dependent RNA polymerase gene and produces an 1135-bp amplicon. This assay was validated using in vitro transcribed RNA and was tested using archived enteric samples collected from turkey flocks in the southeastern United States. Further, a phylogenetic analysis suggests the turkey PBV is unique because it does not group closely with the recognized PBV genogroups circulating in mammalian hosts.


title: Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus.

text: BACKGROUND The role of systemic corticosteroids in the treatment of early childhood wheezing in children is not clear. OBJECTIVE We sought to determine whether prednisolone is effective in rhinovirus-induced early wheezing. METHODS We conducted a controlled trial comparing oral prednisolone (2 mg/kg per day in three divided doses for 3 days) with placebo in 78 hospitalized children (mean age, 1.1 year; standard deviation, 0.7) experiencing their first or second episode of wheezing induced by rhinovirus or respiratory syncytial virus. Mixed viral infections were excluded. Our primary end point was the time until the patient was ready for discharge; secondary end points included oxygen saturation during hospitalization, duration of symptoms, occurrence of relapses during the next 2 months and blood eosinophil counts at discharge and 2 weeks later. RESULTS In multivariate regression analysis, prednisolone did not influence the time until ready for discharge, but it decreased relapses during the subsequent 2-month period in rhinovirus-affected children (prednisolone versus placebo, 22% versus 56%; odds ratio, 19.06; 95% confidence interval, 2.52-144.03; P = 0.004) and in children with blood eosinophils > or = 0.2 x 10/L (respectively, 24% versus 71%; odds ratio, 10.57; 95% confidence interval, 1.99-56.22; P = 0.006). Rhinovirus-affected children had more blood eosinophils on admission (mean, 0.44 versus 0.086 x 10/L), had a higher prevalence of atopy (44% versus 8%) and were older (mean, 1.4 versus 0.9 years, P < 0.001 for all) than respiratory syncytial virus-infected children. CONCLUSION Prednisolone reduced relapses during a 2-month period after first episodes of wheezing associated with rhinovirus infection or blood eosinophils > or = 0.2 x 10/L.


[Yellow fever in Africa].


title: Pathogenicity of turkey astroviruses in turkey embryos and poults.

text: The pathogenicity of turkey astrovirus 2001 (TAstV2001) and turkey astrovirus 1987 (TAstV1987) in specific-pathogen-free (SPF) turkey embryos and commercial poults was investigated. The virus shedding in poults was monitored using electron microscopy (EM) and reverse transcription-polymerase chain reaction (RT-PCR) during the 14-day experimental period. Both viruses caused enteritis and growth depression in SPF turkey embryos and poults. The TAstV2001 did not induce macroscopic or microscopic lesions in thymuses and bursas of embryos or poults. No macroscopic changes were observed in thymuses and bursas of embryos and poults inoculated with TAstV1987, and no statistically significant differences in bursa weight/ body weight ratios (P > 0.05) were detected. However, TAstV1987 infection resulted in microscopic lesions in bursas but not in thymuses of infected embryos and poults. Both TAstV2001 and TAstV1987 were shed during the whole 14-day experimental period as detected by EM and RT-PCR. These findings indicated that both TAstV1987 and TAstV2001 are etiologic agents of turkey enteritis. In addition, TAstV1987 might cause impairment of the immune system of infected poults. The pathogenicity of TAstV1987 is somewhat different from TAstV2001.


Diarrhea associated with Enterococcus faecium in an adult cat.


title: HIPAA administrative simplification: modification to medical data code set standards to adopt ICD-10-CM and ICD-10-PCS. Proposed rule.

text: This proposed rule would modify two of the medical data code set standards adopted in the Transactions and Code Sets final rule published in the Federal Register. It would also implement certain provisions of the Administrative Simplification subtitle of the Health Insurance Portability and Accountability Act (HIPAA) of 1996. Specifically, the proposed rule would modify the standard code sets for coding diagnoses and inpatient hospital procedures by concurrently adopting the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) for diagnosis coding, and the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding. These new codes would replace the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9- CM) Volumes 1 and 2, and the International Classification of Diseases, Ninth Revision, Clinical Modification (CM) Volume 3 for diagnosis and procedure codes, respectively.


Planning for epidemics--the lessons of SARS.


title: Quercetin reduces illness but not immune perturbations after intensive exercise.

text: PURPOSE To investigate the effects of quercetin supplementation on incidence of upper respiratory tract infections (URTI) and exercise-induced changes in immune function. METHODS Trained male cyclists (N=40) were randomized to quercetin (N=20) or placebo (N=20) groups and, under double-blind procedures, received 3 wk quercetin (1000 mg.d(-1)) or placebo before, during, and for 2 wk after a 3-d period in which subjects cycled for 3 h.d(-1) at approximately 57% Wmax. Blood and saliva samples were collected before and after each of the three exercise sessions and assayed for natural killer cell activity (NKCA), PHA-stimulated lymphocyte proliferation (PHA-LP), polymorphonuclear oxidative-burst activity (POBA), and salivary IgA output (sIgA). RESULTS Pre- to postexercise changes in NKCA, PHA-LP, POBA, and sIgA did not differ significantly between quercetin and placebo groups. URTI incidence during the 2-wk postexercise period differed significantly between groups (quercetin=1/20 vs placebo=9/20, Kaplan-Meier analysis statistic=8.31, P=0.004). CONCLUSION Quercetin versus placebo ingestion did not alter exercise-induced changes in several measures of immune function, but it significantly reduced URTI incidence in cyclists during the 2-wk period after intensified exercise.


title: The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant Staphylococcus aureus: a meta-analysis.

text: BACKGROUND Recent guidelines have recommended vancomycin trough levels of 15-20 mg/L for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, high trough levels may increase risk of nephrotoxicity and mortality, and high vancomycin trough levels have not been well studied. This study was designed to combine safety and efficacy results from independent studies and to compare between high and low vancomycin trough levels in the treatment of MRSA-infected patients using meta-analysis. METHODS From 19 eligible studies, 9 studies were included in meta-analysis to compare clinical success between high and low vancomycin trough levels, while 10 and 11 studies met criteria for comparing trough levels and nephrotoxicity and trough levels and mortality, respectively. The PubMed/Medline, Web of Science, and Scopus databases, and hand searching were used to identify eligible studies dated up to March 2016. Of 2344 subjects with MRSA infection, 1036 were assigned to trough levels ≥15 mg/L and 1308 to trough levels <15 mg/L. RESULTS High vancomycin trough levels were found to be associated with risk of nephrotoxicity (odds ratio [OR] 2.14, 95 % confidence interval [CI] 1.42-3.23 and adjusted OR 3.33, 95 % CI 1.91-5.79). There was no evidence of difference between high and low vancomycin trough levels for mortality (OR; 1.09; 95 % CI 0.75-1.60) or clinical success (OR 1.07; 95 % CI 0.68-1.68). CONCLUSION In this study, high vancomycin trough levels were identified as an independent factor associated with risk of nephrotoxicity in MRSA-infected patients. Association between vancomycin trough levels and both adverse effects and clinical outcomes requires further study.


title: Analysis of a 9.6 kb sequence from the 3' end of canine coronavirus genomic RNA.

text: We have analysed the organization of the 3' end of the genomic RNA of canine coronavirus (CCV), a virus which has a close antigenic relationship to transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV) and feline infectious peritonitis virus (FIPV). Genomic RNA isolated from CCV strain Insavc-1-infected A72 cells was used to generate a cDNA library. Overlapping clones, spanning approximately 9.6 kb [from the 3' end of the polymerase gene, 1b, to the poly(A) tail] were identified. Sequencing and subsequent analyses revealed 10 open reading frames (ORFs). Three of these code for the major coronavirus structural polypeptides S, M and N; a fourth codes for a small membrane protein, SM, a putative homologue of the IBV structural polypeptide 3c, and five code for polypeptides, designated 1b, 3a, 4, 7a and 7b, homologous to putative non-structural polypeptides encoded in the TGEV or FIPV genomes. An extra ORF which had not hitherto been identified in this antigenic group of coronaviruses was designated 3x. Pairwise alignment of these ORFs with their counterparts in TGEV, PRCV and FIPV revealed high levels of identity and highlighted the close relationship between the members of this group of viruses.