title: Accurate prediction of human essential genes using only nucleotide composition and association information

text: MOTIVATION: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. AVAILABILITY AND IMPLEMENTATION: http://cefg.uestc.edu.cn/Pheg SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


title: Existence and characterization of allelic variants of Sao, a newly identified surface protein from Streptococcus suis

text: Surface antigen one (Sao) is a newly identified protein from the major zoonotic pathogen, Streptococcus suis. In search of functional proteins related to the pathogenesis of Chinese S. suis 2 (SS2), unexpectedly, a variant of Sao protein was obtained. To test its prevalence in S. suis, PCR assay was adopted to address the coding genes systematically. It was found that there are three allelic variants of sao gene, namely sao-S, sao-M, and sao-L based on the different lengths of the genes (∼1.5, ∼1.7, and ∼2.0 kb, respectively). These differences were determined to be caused by heterogeneity within the number of C-terminal repeat sequences (R), which had been seen as a pathogenicity-related domain in the plant pathogen, Xanthomonas oryzae. Two variants (sao-M and sao-L) were only found in SS2. All three variant proteins were prepared in vitro and their biochemical and biophysical properties were characterized. A soluble form of Sao-M protein was then used as a capture antigen to develop an enzyme-linked immunosorbent assay method to detect antibodies against SS2 in convalescent pig sera. Taken together, the results exhibit the properties of Sao proteins and provide an efficient Sao-M-based method for monitoring SS2 infection.


title: The Transmembrane Region of Microsomal Cytochrome P450 Identified as the Endoplasmic Reticulum Retention Signal(1)

text: Microsomal-type cytochrome P450s are integral membrane proteins bound to the membrane through their N-terminal transmembrane hydrophobic segment, the signal anchor sequence. To elucidate the determinants that enable the P450s to be located in the ER, we constructed cDNAs encoding chimeric proteins in which a secretory form of carboxyesterase, carboxyesterase Sec, was connected to the N-terminus of the full-length or truncated forms of a microsomal-type P450, P45O(M1), and the constructed plasmids were expressed in COS cells. Since carboxyesterase Sec is an iV-glycosylated secretory protein, endo H treatment could be used to determine whether these chimeric proteins were located in the ER or not. Carboxyesterase Sec with the N-terminal 20 amino acids, containing the transmembrane region, of P46O(M1), was located in the ER, as determined from the endo H sensitivity of the expressed protein and immunofluorescence staining of the cells. As the expressed protein exhibited carboxyesterase activity, it was not retained in the ER through the BiP-dependent quality control system recognizing unfolded proteins. Another chimeric protein construct in which carboxyesterase Sec was connected to the C-terminal region of rat UDP-glucuronosyltransferase (UDP-GT), that contained a double-lysin ER retention motif, was also located in the ER, as determined from the endo H sensitivity and immunofluorescence staining. On the other hand, the sugar moiety of the carboxyesterase Sec connected to the transmembrane segment of UDP-GT, Sec/GTd, was partially resistant to the endo H treatment. From the results of immunofluorescent staining and cell fractiona-tion, it was concluded that the Sec/GTd product was located in the Golgi apparatus. These observations indicated that the N-terminal hydrophobic segment of P45O(M1) is sufficient for the ER membrane retention, whereas the transmembrane segment of UDP-GT is not. To determine whether microsomal P450s are recycled between the ER and Golgi compartments or not, a DNA construct encoding cathepsin D connected to the N-terminus of P45O(M1) was prepared and expressed in COS cells. The fusion protein was phosphorylated, but the phosphorylation was sensitive to alkaline phosphatase. As a control, authentic cathepsin D was subjected to phosphorylation of its oligosaccharide chain that was resistant to the alkaline phosphatase treatment. Since GlcNAc-P-transferase, which forms the alkaline phosphatase-resistant phosphodiester in the sugar chains of lysosome-targeting proteins, is located in the Golgi apparatus, it was concluded that the oligosaccharide chain of the cathepsin D portion of the fusion protein was not phosphorylated, and that the chimeric protein did not go to the Golgi apparatus. These results indicate that P45O(M1) is not recycled from the Golgi compartments to the ER in cells.


title: Protective Effect of WC3 Vaccine Against Rotavirus Diarrhea in Infants During a Predominantly Serotype 1 Rotavirus Season

text: We used a double-blind, placebo-controlled trial to study the efficacy of WC3 rotavirus vaccine administered to 104 infants (ages, three to 12 months) before the rotavirus season. Forty-nine infants received vaccine; 55 received placebo. Rotavirus disease during this season was predominantly caused by a serotype 1 strain. In placebo recipients there were 14 cases of rotavirus diarrhea (attack rate, 25%); 11 were moderate to severe (attack rate, 20%). Vaccinees experienced only three cases of rotavirus disease (attack rate, 6.1%), all mild. When all cases (whether associated with rotavirus or not) of clinically significant diarrhea (CSD) were evaluated, WC3 vaccine provided statistically significant (P < .01) protection against the total number of episodes of CSD and reduced the number of days of CSD-associated diarrhea, vomiting, fever, or illness. Seventy-one percent of theWC3vaccinated infants had serum antibody responses to the vaccine. The 14 placebo recipients who experienced natural disease predominantly had antibody responses to serotype 1. Sera taken after the rotavirus season revealed a nearly identical rate (40%) of natural rotavirus infection in the vaccinated and placebo groups.


title: Rhinovirus Infection of Human Embryonic Lung Fibroblasts Induces the Production of a Chemoattractant for Polymorphonuclear Leukocytes

text: Polymorphonuclear leukocytes (PMNLs) appear in the nasal mucosa during rhinovirus colds before the onset of symptoms. This study describes a chemoattractant for PMNLs that is elaborated by human embryonic lung fibroblast cells infected with rhinovirus. Chemotaxis assays were done in a 48-well microchemotaxis chamber with normal adult PMNLs. Medium supernatants from rhinovirus-infected cellculture attracted 87 ± 6 (mean ± SE) PMNLs/10 high-power fields (×450) compared with 38 ± 6 PMNLs/10 highpower fields attracted by medium from uninfected cell cultures (P < .0001). Elaboration of the chemoattractant was not a result of cell destruction and did not require the presence of infectious virus. This chemoattractant produced by human fibroblast cells may contribute to the influx of PMNLs into the nasal mucosa during rhinovirus infection. The PMNLs may, in turn, have a role in producing symptoms of the common cold.


docid: dukauzbf

title: Immunogenicity of Inactivated Influenza Vaccine in Residential Homes for Elderly People

text: One hundred and seventy residents of 11 Leicester City Council homes for the elderly, with a total of 515 beds, were studied during a 30-week period from September 1988 to March 1989 to determine the use of influenza vaccine, the levels of influenza antibody, the incidence of influenza, and the protection afforded by vaccination. The study group of 133 women and 37 men had a mean age of 85 years and 59% had one or more chronic medical conditions. The immunization rates by home for the 170 symptomatic residents ranged from 8% to 90% (mean 45%). Seventy-one sera, 36 from vaccinated and 35 from non-vaccinated residents were collected between 1 December 1988 and 24 March 1989 and were assayed for antibody to A/Taiwan/1/86 (H1N1), A Sichuan/2/87 (H3N2) and B/Beijing/1/87. Analysis revealed no statistically significant differences between the antibody profiles of vaccinated and unvaccinated subjects. Six influenza A and 6 influenza B infections were confirmed among the 170 subjects with upper respiratory tract infections. Influenza vaccination was not associated with significant levels of protection against influenza A or B. Studies of the haemagglutinins of the vaccine strains and influenza isolates during 1988/89 showed that they were closely related.


title: Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges

text: Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID(50)) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID(50) of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo. There were also statistically significant reductions in the mean total nasal secretion weights and total tissue counts. Zinc, however, had no significant effect on the rate or amount of virus excreted by volunteers. We conclude that zinc gluconate lozenges are reasonably well tolerated and that they have a significant effect on the signs and symptoms of colds caused by rhinoviruses, although the mechanism of action remains obscure.


title: Xanthine Oxidase Inhibition by Febuxostat in Macrophages Suppresses Angiotensin II-Induced Aortic Fibrosis

text: BACKGROUND: Several reports from basic researches and clinical studies have suggested that xanthine oxidase (XO) inhibitors have suppressive effects on cardiovascular diseases. However, the roles of a XO inhibitor, febuxostat (FEB), in the pathogenesis of vascular remodeling and hypertension independent of the serum uric acid level remain unclear. METHODS: To induce vascular remodeling in mice, angiotensin II (Ang II) was infused for 2 weeks with a subcutaneously implanted osmotic minipump. FEB was administered every day during Ang II infusion. Aortic fibrosis was assessed by elastica van Gieson staining. Mouse macrophage RAW264.7 cells (RAW) and mouse embryonic fibroblasts were used for in vitro studies. RESULTS: FEB suppressed Ang II-induced blood pressure elevation and aortic fibrosis. Immunostaining showed that Ang II-induced macrophage infiltration in the aorta tended to be suppressed by FEB, and XO was mainly colocalized in macrophages, not in fibroblasts. Transforming growth factor-β1 (TGF-β1) mRNA expression was induced in the aorta in the Ang II alone group, but not in the Ang II + FEB group. Ang II induced α-smooth muscle actin-positive fibroblasts in the aortic wall, but FEB suppressed them. XO expression and activity were induced by Ang II stimulation alone but not by Ang II + FEB in RAW. FEB suppressed Ang II-induced TGF-β1 mRNA expression in RAW. CONCLUSIONS: Our results suggested that FEB ameliorates Ang II-induced aortic fibrosis via suppressing macrophage-derived TGF-β1 expression.


title: ROTAVIRUS INFECTION IN ELDERLY PATIENTS

text: In the course of an outbreak of non-bacterial diarrhoea in a group of elderly patients in a rehabilitation ward, rotavirus was detected by electron-microscopy in five of 11 stool specimens (45.5%) from symptomatic elderly patients. This suggests that although rotavirus is usually thought of as a cause of gastro-enteritis in children it should also be considered as a cause of non-bacterial diarrhoea in elderly patients and stool specimens examined for its presence. Rotavirus gastro-enteritis appears to be a highly contagious disease but appropriate measures can limit its spread.


title: Comparison of expression vectors in Lactobacillus reuteri strains

text: The synthesis of heterologous proteins in lactobacilli is strongly influenced by the promoter selected for the expression. In addition, the activity of the promoters themselves may vary among different bacterial hosts. Three different promoters were investigated for their capability to drive enhanced green fluorescent protein (EGFP) expression in Lactococcus lactis spp. cremoris MG1363, in Lactobacillus reuteri DSM 20016(T) and in five L. reuteri strains isolated from chicken crops. The promoters of the Lactobacillus acidophilus surface layer protein gene (slp), L. acidophilus lactate dehydrogenase gene (ldhL) and enterococcal rRNA adenine N-6-methyltransferase gene (ermB) were fused to the coding sequence of EGFP and inserted into the backbone of the pTRKH3 shuttle vector (pTRKH3-slpGFP, pTRKH3-ldhGFP, pTRKH3-ermGFP). Besides conventional analytical methods, a new quick fluorimetric approach was set up to quantify the EGFP fluorescence in transformed clones using the Qubit(™) fluorometer. ermB proved to be the most effective promoter in L. reuteri isolates, producing 3.90 × 10(−7) g of fluorescent EGFP (mL OD(stationary culture))(−1). Under the same conditions, the ldhL promoter produced 2.66 × 10(−7) g of fluorescent EGFP (mL OD(stationary culture))(−1). Even though the slp promoter was efficient in L. lactis spp. cremoris MG1363, it was nearly inactive both in L. reuteri DSM 20016(T) and in L. reuteri isolates.


docid: knbyjvua

title: Isoprinosine: Lack of Antiviral Activity in Experimental Model Infections

text: This report is a condensation of data from a collaborative study proposed and sponsored by the Antiviral Substances Program of NIAID. The individual reports were prepared by the following persons: S. Baron and M. Worthington, NIAID, NIH; A. Friedman-Kien, New York University College of Medicine; J. C. Duenwald, Washington State University, L. A. Glasgow, M. Harmon, B. Janis, E. Kern, J. C. Overall, Jr., C. B. Smith, D. A. Stringfellow, and S. Westerberg, University of Utah College of Medicine; B. C. Easterday and E. H. Weinberg, University of Wisconsin.* Recently there has been much interest in isoprinosine as a broad-spectrum antiviral compound. The activity of this substance was evaluated in a coordinated study at five institutions. Experimental models in five species of animals were established using 11 viruses. Criteria for selection were: (l) representation of most major groups of viruses, (2) reproduction of natural routes of infection, and (3) simulation of potentially treatable viral infections of man. No therapeutic effect could be demonstrated in infections with encephalomyocarditis virus, type 2 Herpesvirus hominis, influenza, and rabies viruses in mice; vaccinia virus in rabbits; rhinotracheitis and panleukopenia viruses in cats; distemper virus in ferrets; and influenza and transmissible gastroenteritis viruses in swine. The only antiviral activity observed in this extensive series of experiments was suppression of fibroma virus lesions in rabbits given 600 mg/ kg per day of isoprinosine. Although antiviral activity is not precluded in other viral infections in animals or in man, these results clearly fail to substantiate the potential of isoprinosine as a potent, broad-spectrum antiviral substance.


title: Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules

text: New strategies applied in the treatment of experimental autoimmune disease models involve blocking or modulation of MHC–peptide–TCR interactions either at the level of peptide–MHC interaction or, alternatively, at the level of T cell recognition. In order to identify useful competitor peptldes one must be able to assess peptide–MHC interactions. Several well described autoimmune disease models exist in the Lewis rat and thus this particular rat strain provides a good model system to study the effect of competitor peptldes. So far no information has been available on the peptide binding characteristics of the Lewis rat MHC class II RT1.B(I) molecule. We have now developed a biochemical binding assay which enables competition studies in which the relative MHC binding affinity of a set of non-labelled peptldes can be assessed while employing detection of blotlnylated marker peptides by chemllumlnescence. The assay is sensitive and specific. We have used this assay to determine the binding characteristics of several disease associated T cell determinants and their sequence analogues in the Lewis rat. Notably, most of the autoimmune disease associated peptide sequences tested were found to be intermediate to poor binders. Single amino acid substitutions at defined positions were sufficient to turn certain peptldes into good binders. These results are relevant to the design of competitor peptldes in the treatment of experimental autoimmune diseases.


Infectious diseases pharmacy residency programs


Tracheostomy in a patient with SARS


title: Severity of Pneumonia Due to New H1N1 Influenza Virus in Ferrets Is Intermediate between That Due to Seasonal H1N1 Virus and Highly Pathogenic Avian Influenza H5N1 Virus

text: Background. The newly emerged influenza A(H1N1) virus (new H1N1 virus) is causing the first influenza pandemic of this century. Three influenza pandemics of the previous century caused variable mortality, which largely depended on the development of severe pneumonia. However, the ability of the new H1N1 virus to cause pneumonia is poorly understood. Methods. The new H1N1 virus was inoculated intratracheally into ferrets. Its ability to cause pneumonia was compared with that of seasonal influenza H1N1 virus and highly pathogenic avian influenza (HPAI) H5N1 virus by using clinical, virological, and pathological analyses. Results. Our results showed that the new H1N1 virus causes pneumonia in ferrets intermediate in severity between that caused by seasonal H1N1 virus and by HPAI H5N1 virus. The new H1N1 virus replicated well throughout the lower respiratory tract and more extensively than did both seasonal H1N1 virus (which replicated mainly in the bronchi) and HPAI H5N1 virus (which replicated mainly in the alveoli). High loads of new H1N1 virus in lung tissue were associated with diffuse alveolar damage and mortality. Conclusions. The new H1N1 virus may be intrinsically more pathogenic for humans than is seasonal H1N1 virus.


docid: emmoeuqd

title: An Impaired Breeding Phenotype in Mice with a Genetic Deletion of Beta-2 Microglobulin and Diminished MHC Class I Expression: Role in Reproductive Fitness(1)

text: Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals, including its association with major histocompatibility complex (MHC) Class I gene products. The latter molecules have been shown to affect reproduction in both mice and humans, although the exact mechanism is still unknown. Here we report the results of a longitudinal study of the reproductive performance of a genetically modified B2m deficient mouse strain with low MHC Class I expression. Our data show that this mouse strain has an impaired reproductive performance. However, the mice superovulate well and show a normal estrous cycle. Breeding studies from crosses between the transgenic mice and the wild-type parental strain show that B2m deficient mice have a significantly lower frequency of mating than the control B2m(+/+) mice. In addition, the litter size and weaning success of B2m deficient mice were lower than the control. Perinatal lethality of the B2m deficient offspring was also inflicted by cannibalism of the young pups by the B2m deficient female. The impaired breeding phenotype (IBP) can be reversed by reintroducing the B2m gene in F1 heterozygous B2m(+/−) animals; thus the presence of B2M confers a normal breeding pattern. The acquisition of an impaired breeding phenotype (IBP) as a result of the knockout of B2m directly implicates B2M in the reproductive cycle of mice and raises the possibility of an effect of B2M on the reproduction of other mammals.


title: Design of peptide inhibitors for furin based on the C‐terminal fragment of histone H1.2

text: The mammalian proprotein convertase furin has been found to play an important role in diverse physiological and pathological events, such as the activation of viral glycoproteins and bacterial exotoxins. Small, non‐toxic and highly active, furin inhibitors are considered to be attractive drug candidates for diseases caused by virus and bacteria. In this study, a series of peptide inhibitors were designed and synthesized based on the C‐terminal fragment of histone H1.2, which has an inhibitory effect on furin. Replacing the reactive site of inhibitors with the consensus substrate recognition sequence of furin has been found to increase inhibitory activity greatly. The most potent inhibitor, I(4), with 14 amino acid residues has a K(i) value of 17 nM for furin. Although most of the synthesized peptides were temporary inhibitors, the inhibitor I(5), with nine amino acids, retained its full potency, even after a 3 h incubation period with furin at 37 °C. These inhibitors may potentially lead to the development of anti‐viral and antibacterial drug compounds.


Coronaviruses in the Limelight


The enteric flora in childhood disease —diarrhea


title: Human G-CSF synthesis using stress-responsive bacterial proteins

text: We previously reported that under the stress condition caused by the addition of 2-hydroxyethyl disulfide, a thiol-specific oxidant, to growing cultures of Escherichia coli BL21(DE3), a population of stress-responsive proteins [peptidyl-prolyl cis–trans isomerase B (PpiB), bacterioferritin (Bfr), putative HTH-type transcriptional regulator yjdC (YjdC), dihydrofolate reductase (FolA), chemotaxis protein cheZ (CheZ), and glutathione synthetase (GshB)] were significantly upregulated when compared with the nonstress condition. When those stress-responsive proteins were used as fusion partners for the expression of human granulocyte colony-stimulating factor (hG-CSF), the solubility of hG-CSF was dramatically enhanced in E. coli cytoplasm, whereas almost all of the directly expressed hG-CSF were aggregated to inclusion bodies. In addition, the spectra of circular dichroism measured with the purified hG-CSF were identical to that of standard hG-CSF, implying that the synthesized hG-CSF has native conformation. These results indicate that the bacterial stress-responsive proteins could be potent fusion expression partners for aggregation-prone heterologous proteins in E. coli cytoplasm.


title: Analysis of the Interaction of Ebola Virus Glycoprotein with DC-SIGN (Dendritic Cell—Specific Intercellular Adhesion Molecule 3—Grabbing Nonintegrin) and Its Homologue DC-SIGNR

text: Background. The lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) augments Ebola virus (EBOV) infection. However, it its unclear whether DC-SIGN promotes only EBOV attachment (attachment factor function, nonessential) or actively facilitates EBOV entry (receptor function, essential). Methods. We investigated whether DC-SIGN on B cell lines and dendritic cells acts as an EBOV attachment factor or receptor. Results. Engineered DC-SIGN expression rendered some B cell lines susceptible to EBOV glycoprotein (EBOV GP)-driven infection, whereas others remained refractory, suggesting that cellular factors other than DC-SIGN are also required for susceptibility to EBOV infection. Augmentation of entry was independent of efficient DCSIGN internalization and might not involve lectin-mediated endocytic uptake of virions. Therefore, DC-SIGN is unlikely to function as an EBOV receptor on B cell lines; instead, it might concentrate virions onto cells, thereby allowing entry into cell lines expressing low levels of endogenous receptor(s). Indeed, artificial concentration of virions onto cells mirrored DC-SIGN expression, confirming that optimization of viral attachment is sufficient for EBOV GP-driven entry into some B cell lines. Finally, EBOV infection of dendritic cells was only partially dependent on mannose-specific lectins, such as DC-SIGN, suggesting an important contribution of other factors. Conclusions. Our results indicate that DC-SIGN is not an EBOV receptor but, rather, is an attachmentpromoting factor that boosts entry into B cell lines susceptible to low levels of EBOV GP-mediated infection.


title: Inhibition of Rhinovirus Replication In Vitro and In Vivo by Acid-Buffered Saline

text: Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus. Preliminary experiments verified that the surface pH of the human nasopharynx could be transiently lowered to pH ∼4.0 by topical administration of citrate/phosphate (CP) buffers, which was well tolerated. In a pilot experimental colds study, intranasal administration of CP buffer, compared with normal saline, reduced viral shedding by 1 log unit (10(3) vs. 10(4) 50%tissue culture infective dose/mL; P < .01), although respiratory symptoms were not significantly reduced. These findings demonstrate that low-pH buffers have antiviral activity in vivo and suggest that a larger clinical trial is warranted to determine whether this approach could reduce rates of viral transmission.


title: Pepitope: epitope mapping from affinity-selected peptides

text: Identifying the epitope to which an antibody binds is central for many immunological applications such as drug design and vaccine development. The Pepitope server is a web-based tool that aims at predicting discontinuous epitopes based on a set of peptides that were affinity-selected against a monoclonal antibody of interest. The server implements three different algorithms for epitope mapping: PepSurf, Mapitope, and a combination of the two. The rationale behind these algorithms is that the set of peptides mimics the genuine epitope in terms of physicochemical properties and spatial organization. When the three-dimensional (3D) structure of the antigen is known, the information in these peptides can be used to computationally infer the corresponding epitope. A user-friendly web interface and a graphical tool that allows viewing the predicted epitopes were developed. Pepitope can also be applied for inferring other types of protein–protein interactions beyond the immunological context, and as a general tool for aligning linear sequences to a 3D structure. Availability: http://pepitope.tau.ac.il/ Contact: talp@post.tau.ac.il


title: Assessment of the Status of Measles Elimination in the United States, 2001–2014

text: We assessed the status of measles elimination in the United States using outbreak notification data. Measles transmissibility was assessed by estimation of the reproduction number, R, the average number of secondary cases per infection, using 4 methods; elimination requires maintaining R at <1. Method 1 estimates R as 1 minus the proportion of cases that are imported. Methods 2 and 3 estimate R by fitting a model of the spread of infection to data on the sizes and generations of chains of transmission, respectively. Method 4 assesses transmissibility before public health interventions, by estimating R for the case with the earliest symptom onset in each cluster (R(index)). During 2001–2014, R and R(index) estimates obtained using methods 1–4 were 0.72 (95% confidence interval (CI): 0.68, 0.76), 0.66 (95% CI: 0.62, 0.70), 0.45 (95% CI: 0.40, 0.49), and 0.63 (95% CI: 0.57, 0.69), respectively. Year-to-year variability in the values of R and R(index) and an increase in transmissibility in recent years were noted with all methods. Elimination of endemic measles transmission is maintained in the United States. A suggested increase in measles transmissibility since elimination warrants continued monitoring and emphasizes the importance of high measles vaccination coverage throughout the population.


title: Alanyl Aminopeptidase from Human Seminal Plasma: Purification, Characterization, and Immunohistochemical Localization in the Male Genital Tract(1)

text: Alanyl aminopeptidase (AAP) was purified to homogeneity from human seminal plasma. The calculated molecular weight of the purified enzyme was approximately 137,000±5,000 from light scattering, 140,000 (main) and 137,000 (minor) from non-denatured PAGE and 153,000 from SDS-PAGE in the absence or presence of 2-mercaptoethanol (2-ME). These findings suggest that the enzyme is monomeric in form in human seminal plasma. The enzyme hydrolyzed several amino acid 4-methyl-coumaryl-7-amide (MCA) substrates. The order of K(cat;)/K(m) values of AAP at optimal pH (pH 7.5) was Ala- >Lys-Ala- ≥ Met- > Leu- > Phe- > Arg- ≥ Arg-Arg- > Lys- > Gly-MCAs. AAP was potently inhibited by bestatin, leuhis-tin, actinonin, amastatin, and 1,10-phenanthroline. These findings suggest that AAP is an aminopeptidase. We determined that the amino acid sequence of the first 22 residues of the enzyme was Ser(1)-Thr-Thr-Pro-Ser(5)-Ala-Ser-Ala-Thr-Thr(10)-Asn-Pro-Ala-Ser-Ala(15)-Thr-Thr-Leu-Asp-Gln(20)-Ser-Lys-. This sequence was completely coincident with that downstream of the transmembrane site of human intestinal alanyl aminopeptidase N (CD13). We also isolated cDNA encoding AAP from human prostate cDNA library, sequenced its structure, and confirmed human seminal plasma AAP to be identical with alanyl aminopeptidase N. We postulated that native human seminal plasma alanyl aminopeptidase is released into the seminal plasma after the specific site is cleaved by elastase or an elastase-like enzyme. The enzyme level in human seminal plasma determined by single radial immunodiffusion was 5.2±3.2mg/100ml (mean±SD, n=20) in individuals 20–47 years of age. AAP was immunohistochemically stained in the luminal site-cell membrane of epithelial cells in the prostatic gland and ductuli efferentes of the testis.


docid: ljayoodm

title: Ecology of Avian Influenza Virus in Birds

text: Avian influenza A virus (an orthomyxovirus) is a zoonotic pathogen with a natural reservoir entirely in birds. The influenza virus genome is an 8-segment single-stranded RNA with high potential for in situ recombination. Two segments code for the hemagglutinin (H) and neuraminidase (N) antigens used for host-cell entry. At present, 16 H and 9 N subtypes are known, for a total of 144 possible different influenza subtypes, each with potentially different host susceptibility. With >10,000 species of birds found in nearly every terrestrial and aquatic habitat, there are few places on earth where birds cannot be found. The avian immune system differs from that of humans in several important features, including asynchronous B and T lymphocyte systems and a polymorphic multigene immune complex, but little is known about the immunogenetics of pathogenic response. Postbreeding dispersal and migration and a naturally high degree of environmental vagility mean that wild birds have the potential to be vectors that transmit highly pathogenic variants great distances from the original sources of infection.


title: Loop-mediated isothermal amplification method for rapid detection of the toxic dinoflagellate Alexandrium, which causes algal blooms and poisoning of shellfish

text: The marine dinoflagellate genus Alexandrium includes a number of species that produce potent neurotoxins responsible for paralytic shellfish poisoning, which in humans may cause muscular paralysis, neurological symptoms and, in extreme cases, death. Because of the genetic diversity of different genera and species, molecular tools may help to detect the presence of target microorganisms in marine field samples. Here we employed a loop-mediated isothermal amplification (LAMP) method for the rapid and simple detection of toxic Alexandrium species. A set of four primers were designed based upon the conserved region of the 5.8S rRNA gene of members of the genus Alexandrium. Using this detection system, toxic Alexandrium genes were amplified and visualized as a ladder-like pattern of bands on agarose gels under isothermal condition within 60 min. The LAMP amplicons were also directly visualized by eye in the reaction tube by the addition of SYBR Green I. This LAMP assay was 10-fold more sensitive than a conventional PCR method with a detection limit of 5 cells per tube when targeting DNA from Alexandrium minutum. The LAMP assay reported here indicates the potential usefulness of the technique as a valuable simple, rapid alternative procedure for the detection of target toxic Alexandrium species during coastal water monitoring.


title: Interferon-beta treatment increases human papillomavirus early gene transcription and viral plasmid genome replication by activating interferon regulatory factor (IRF)-1

text: Interferons (IFNs) have been used to treat mucosal lesions caused by human papillomavirus (HPV) infection, such as intraepithelial precursor lesions to cancer of the uterine cervix, genital warts or recurrent respiratory papillomatosis, to potentially reduce or eliminate replicating HPV plasmid genomes. Mucosal HPVs have evolved mechanisms that impede IFN-β synthesis and downregulate genes induced by IFN. Here we show that these HPV types directly subvert a cellular transcriptional response to IFN-β as a potential boost in infection. Treatment with low levels of human IFN-β induced initial amplification of HPV-16 and HPV-11 plasmid genomes and increased HPV-16 or HPV-31 DNA copy numbers up to 6-fold in HPV-immortalized keratinocytes. IFN treatment also increased early gene transcription from the major early gene promoters in HPV-16, HPV-31 and HPV-11. Furthermore, mutagenesis of the viral genomes and ectopic interferon regulatory factor (IRF) expression in transfection experiments using IRF-1 (−/−) , IRF-2 (−/−) and dual knockout cell lines determined that these responses are due to the activation of IRF-1 interaction with a conserved interferon response element demonstrated in several mucosal HPV early gene promoters. Our results provide a molecular explanation for the varying clinical outcomes of IFN therapy of papillomatoses and define an assay for the modulation of the HPV gene program by IFNs as well as other cytokines and signaling molecules in infection and therapy.


title: Leukocyte Interferon for Treating First Episodes of Genital Herpes in Women

text: Women experiencing their first episodes of genital herpes were treated, beginning within three days of the onset of lesions, with 5 × 10(4) units of human leukocyte interferon/kg of body weight for 12 doses over 14 days (total, ∼3.6 × 10(7) units) or with placebo in equivalent volumes. Life-table analysis revealed quicker healing and significant reductions in the duration of shedding of virus in interferon-treated patients. Maximum daily geometric mean titers of virus and total area of unhealed lesions also decreased more quickly. No statistically significant difference in resolution of pain was seen between the two groups. Interferon had no effect on onset or frequency of subsequent recurrences recorded over one year of follow-up. Moderate, transient neutropenia occurred in 13 of 34 interferon-treated patients. A therapeutic effect of human leukocyte interferon on initial genital herpes was documented, but the clinical usefulness of interferon treatment of genital herpes is limited at this time.


title: Human Calicivirus-Associated Diarrhea In Children Attending Day Care Centers

text: We investigated human calicivirus (HCV)-associated diarrheain children attending day care centers by using stool specimens collected in 1981–1983. We used a screening enzyme linked immunosorbent assay (ELISA) derived from reagents prepared against the Sapporostrain ofHCV and confirmed positive results with a blocking ELISA an dimmunosorbent electron microscopy. HCV was detected in 11 (2.9%) of 375 diarrheal stools and in none of 86 stools from asymptomatic contacts. This incidence ratewas half that noted for rotaviruses and higher than that noted for Campylobaeter, Salmonella, and Shigella in the original study. HCV was found in stool specimens from children in nine day care centers; HCV-associated diarrhea was sporadic, occurred with greater frequency in young children, and had a summer-fall predominance. Our results indicate that HeV is an important cause of diarrheain day care centers and that frozen stool samples can yield epidemiological data on HCV infection.


New treatments for viral respiratory tract infections—opportunities and problems


Surveillance of imported infectious diseases in Europe: report from the 4th TropNetEurop workshop


Pneumocystis carinii in Germ-Free Rats


title: A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients

text: Both genetic variants and messenger RNA (mRNA) expression of DNA repair and tumor suppressor genes have been investigated as molecular markers for therapy outcome. However, the phenotypic impact of genetic variants often remained unclear, thus the rationale of their use in risk prediction may be limited. We therefore analyzed genetic variants together with anthropometric and lifestyle factors to see how these affect mRNA levels of ERCC1 , MDM2 and TP53 in primary blood lymphocytes. mRNA expression was measured in 376 prostate cancer patients by quantitative real-time polymerase chain reaction after reverse transcription, and ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and TP53 rs17878362 (p53PIN3) polymorphisms were determined. Considerable interindividual differences in mRNA expression were found (coefficients of variation: ERCC1 , 45%; MDM2 , 43% and TP53 , 35%). ERCC1 expression was positively correlated with plasma levels of β-carotene ( P = 0.03) and negatively correlated with canthaxanthin ( P = 0.02) and lutein ( P = 0.02). Overall, the polymorphisms affected mRNA expression only weakly. Carriers of a distinct ERCC1 haplotype (CC) showed, however, significantly lower expression values than non-carriers ( P = 0.001). Applying logistic regression, we found that CC haplotype carriers had a 1.69-fold increased odds ratio (95% confidence interval: 1.06–2.71) for reduced ERCC1 mRNA levels. This low ERCC1 expression might be associated with reduced DNA repair and better therapy response. In summary, the association we have found between ERCC1 genotype and mRNA expression supports recent clinical observations that genetic variation in ERCC1 can affect treatment outcome and prognosis. Our study further revealed a modulating effect by nutritional factors.


title: A COMPARISON OF SUBCUTANEOUS, NASAL, AND COMBINED INFLUENZA VACCINATION. II. PROTECTION AGAINST NATURAL CHALLENGE(1)(2)

text: Edmondson, W. P., Jr., R. Rothenberg, P. W. White and J. M. Gwaltney, Jr. (Univ. of Virginia School of. Medicine, Charlottesville, Va. 22901). A comparison of subcutaneous, nasal, and combined influenza vaccination. II. Protection against natural challenge. Amer J Epidem 93: 480–486, 1971.—Monovalent killed influenza A(2) Hong Kong vaccine in doses (400 CCA units) recommended for civilian use was given to insurance company employees and elderly psychiatric patients by injection, nasal spray, or a combination of both methods. Vaccinees and controls were then studied for evidence of immunity to influenza during the 1968–1969 epidemic Parenteral vaccination was well tolerated and effective in reducing influenza infection and illness rates in both groups. Vaccine had no effect on total respiratory illness in the insurance group, although total absenteeism was lowered because of the greater effect of influenza over that of colds in causing time lost from work. Vaccine given by spray into the respiratory tract was ineffective. The addition of spray to parenteral vaccination provided no additional advantage over parenteral vaccination alone.


title: Pre- and Postexposure Use of Human Monoclonal Antibody against H5N1 and H1N1 Influenza Virus in Mice: Viable Alternative to Oseltamivir

text: New strategies to prevent and treat influenza virus infections are urgently needed. A recently discovered class of monoclonal antibodies (mAbs) neutralizing an unprecedented spectrum of influenza virus subtypes may have the potential for future use in humans. Here, we assess the efficacies of CR6261, which is representative of this novel class of mAbs, and oseltamivir in mice. We show that a single injection with 15 mg/kg CR6261 outperforms a 5-day course of treatment with oseltamivir (10 mg/kg/day) with respect to both prophylaxis and treatment of lethal H5N1 and H1N1 infections. These results justify further preclinical evaluation of broadly neutralizing mAbs against influenza virus for the prevention and treatment of influenza virus infections


title: Variant Effect of First- and Second-Generation Antihistamines as Clues to Their Mechanism of Action on the Sneeze Reflex in the Common Cold

text: Treatment with first-generation antihistamines reduces sneezing, rhinorrhea, nasal mucus weight, and, in some instances, cough in subjects with experimental or natural colds; however, treatment with second-generation antihistamines has not been effective for these complaints in trials in subjects with natural colds. This article reports the negative results of a clinical trial with loratadine, a second-generation antihistamine, in adults in the rhinovirus challenge model. This finding in the highly controlled setting of the challenge model confirms the earlier negative studies with second-generation antihistamines in natural colds. First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier. Second-generation antihistamines mainly block histaminic receptors and do not pass the blood-brain barrier. The effectiveness of first-generation antihistamines in blocking sneezing in colds may be due primarily to neuropharmacological manipulation of histaminic and muscarinic receptors in the medulla.


title: A compendium of small molecule direct-acting and host-targeting inhibitors as therapies against alphaviruses

text: Alphaviruses were amongst the first arboviruses to be isolated, characterized and assigned a taxonomic status. They are globally widespread, infecting a large variety of terrestrial animals, birds, insects and even fish. Moreover, they are capable of surviving and circulating in both sylvatic and urban environments, causing considerable human morbidity and mortality. The re-emergence of Chikungunya virus (CHIKV) in almost every part of the world has caused alarm to many health agencies throughout the world. The mosquito vector for this virus, Aedes, is globally distributed in tropical and temperate regions and capable of thriving in both rural and urban landscapes, giving the opportunity for CHIKV to continue expanding into new geographical regions. Despite the importance of alphaviruses as human pathogens, there is currently no targeted antiviral treatment available for alphavirus infection. This mini-review discusses some of the major features in the replication cycle of alphaviruses, highlighting the key viral targets and host components that participate in alphavirus replication and the molecular functions that were used in drug design. Together with describing the importance of these targets, we review the various direct-acting and host-targeting inhibitors, specifically small molecules that have been discovered and developed as potential therapeutics as well as their reported in vitro and in vivo efficacies.


title: Differential Expression of Chemokines and Their Receptors in Adult and Neonatal Macrophages Infected with Human or Avian Influenza Viruses

text: In 1997, avian influenza virus H5N1 was transmitted directly from chicken to human and resulted in a severe disease that had a higher mortality rate in adults than in children. The characteristic mononuclear leukocyte infiltration in the lung and the high inflammatory response in H5N1 infection prompted us to compare the chemokine responses between influenza virus–infected adult and neonatal monocyte-derived macrophages (MDMs). The effects of avian influenza virus A/Hong Kong/483/97 (H5N1) (H5N1/97), its precursor A/Quail/Hong Kong/G1/97 (H9N2) (H9N2/G1), and human influenza virus A/Hong Kong/54/98 (H1N1) (H1N1/98) were compared. Significantly higher expression of CCL2, CCL3, CCL5, and CXCL10 was induced by avian influenza viruses than by human influenza virus. Moreover, the increase in CCL3 expression in H5N1/97-infected adult MDMs was significantly higher than that in neonatal MDMs. Enhanced expression of CCR1 and CCR5 was found in avian virus–infected adult MDMs. The strong induction of chemokines and their receptors by avian influenza viruses, particularly in adult MDMs, may account for the severity of H5N1 disease


title: Host and Viral Factors Affecting the Decreased Immunogenicity of Sabin Type 3 Vaccine after Administration of Trivalent Oral Polio Vaccine to Rural Mayan Children

text: Factors affecting immunogenicity of the first 2 doses of oral poliovirus vaccine (OPV) among unimmunized Mayan infants were prospectively evaluated. The relative impact of multiple variables, including mass or routine vaccination, concurrent enteric bacterial (salmonella, shigella, and campylobacter) and viral (adenovirus 40/41, astrovirus, nonpolio enteroviruses, and rotavirus) infections, interference among Sabin vaccine viruses, and preexisting poliovirus antibodies were studied. Sera were available from 181 infants after 2 OPV doses. Seroresponses were 86% to Sabin type 1, 97% to Sabin type 2, and 61% to Sabin type 3 vaccines. Mass versus routine vaccination and preexisting poliovirus antibodies did not affect immunogenicity. By multiple logistic regression analysis, fecal shedding of homologous Sabin strains was associated with increased seroresponses to all Sabin types, especially to Sabin type 3. Decreased OPV immunogenicity was primarily attributable to interference of Sabin type 3 by Sabin type 2. OPV formulations with higher doses of Sabin type 3 could improve immunogenicity among infants in developing countries.


title: The state of play in the battle against antimicrobial resistance: a general practitioner perspective

text: This article summarizes personal reflections from the perspective of general practice on developments with regard to antibiotic resistance and the containment of antibiotic prescribing during the lifetime of the Specialist Advisory Committee on Antimicrobial Resistance in England. These reflections concern the entry of antibiotics into the food chain, recent extensions of prescribing responsibilities and developments towards improved surveillance and reduced antibiotic prescribing. A large gap remains between the scientific appreciation of the risks from antimicrobial resistance and effective means to measure it and thereby hopefully control it.


title: Modeling the adaptive immune system: predictions and simulations

text: Motivation: Immunological bioinformatics methods are applicable to a broad range of scientific areas. The specifics of how and where they might be implemented have recently been reviewed in the literature. However, the background and concerns for selecting between the different available methods have so far not been adequately covered. Summary: Before using predictions systems, it is necessary to not only understand how the methods are constructed but also their strength and limitations. The prediction systems in humoral epitope discovery are still in their infancy, but have reached a reasonable level of predictive strength. In cellular immunology, MHC class I binding predictions are now very strong and cover most of the known HLA specificities. These systems work well for epitope discovery, and predictions of the MHC class I pathway have been further improved by integration with state-of-the-art prediction tools for proteasomal cleavage and TAP binding. By comparison, class II MHC binding predictions have not developed to a comparable accuracy level, but new tools have emerged that deliver significantly improved predictions not only in terms of accuracy, but also in MHC specificity coverage. Simulation systems and mathematical modeling are also now beginning to reach a level where these methods will be able to answer more complex immunological questions. Contact: lunde@cbs.dtu.dk Supplementary information: Supplementary data are available at Bioinformatics online.


title: Cross-Protection against H5N1 Influenza Virus Infection Is Afforded by Intranasal Inoculation with Seasonal Trivalent Inactivated Influenza Vaccine

text: Background. Avian H5N1 influenza A virus is an emerging pathogen with the potential to cause substantial human morbidity and mortality. We evaluated the ability of currently licensed seasonal influenza vaccine to confer cross-protection against highly pathogenic H5N1 influenza virus in mice. Methods. BALB/c mice were inoculated 3 times, either intranasally or subcutaneously, with the trivalent inactivated influenza vaccine licensed in Japan for the 2005–2006 season. The vaccine included A/NewCaledonia/20/99 (H1N1), A/NewYork/55/2004 (H3N2), and B/Shanghai/361/2002 viral strains and was administered together with poly(I):poly(C(12)U) (Ampligen) as an adjuvant. At 14 days after the final inoculation, the inoculated mice were challenged with either the A/HongKong/483/97, the A/Vietnam/1194/04, or the A/Indonesia/6/05 strain of H5N1 influenza virus. Results. Compared with noninoculated mice, those inoculated intranasally manifested cross-reactivity of mucosal IgA and serum IgG with H5N1 virus, as well as both a reduced H5N1 virus titer in nasal-wash samples and increased survival, after challenge with H5N1 virus. Subcutaneous inoculation did not induce a cross-reactive IgA response and did not afford protection against H5N1 viral infection. Conclusions. Intranasal inoculation with annual influenza vaccine plus the Toll-like receptor—3 agonist, poly(I): poly(C(12)U), may overcome the problem of a limited supply of H5N1 virus vaccine by providing cross-protective mucosal immunity against H5N1 viruses with pandemic potential.


The Pandemic Requires a Coordinated Global Economic Response


docid: wuuhlowd

title: The Finnish Pension System and Its Future Challenges

text: A specific feature in the Finnish pension system is rule-based preparation for mortality change. The earned pension capital is adjusted to life expectancy and the lowest age limit of the flexible retirement age will be adapted so that the ratio of expected years in employment and retirement is fixed after year 2030.


in the final analysis


docid: pkjfnhro

title: Leukonychia Partialis in Kawasaki Disease


title: Food Restriction Differentially Affects mRNAs Encoding the Major Anterior Pituitary Tropic Hormones

text: Chronic food restriction (FR) leads to adaptive cellular changes, some of which retard aging. Moreover, some of these changes occur within weeks after onset of FR. Because neuroendocrine mechanisms may mediate these effects, we measured the effect of FR on the messenger ribonucleicacids (mRNAs) encoding all of the tropic hormones of the anterior pituitary (AP). Slot blot and solution hybridization were conducted on AP ribonucleicacid (RNA) samples obtained at 0500 h (AM) and 1500 h (PM) from 3-month-old male Fischer 344 rats fed ad libitum (AL) or FR (60% of AL calories) since 6 weeks of age. Poly A RNA/μg total RNA was similar in AL and FR rats, indicating that there was no overall effect of FR on mRNA levels. The level of proopiomelanocortin (POMC) mRNA was not reduced by FR when expressed per fig of RNA or as total AP content. By contrast, the total AP content of the mRNAs encoding LHβ, FSHβ TSHβ, GH, and PRL was markedly reduced by FR. When expressed per fig of RNA, however, only GH (AM and PM), FSHβ (AM), TSHbeta; (PM), and PRL (PM) were reduced by FR. These results reveal that FR differentially affects pituitary tropic hormone mRNA levels within weeks after onset of FR, and are consistent with a role for neuroendocrine alterations in the initiation of adaptive cellular responses to FR.


title: Pathologic Characterization of Brown Norway, Brown Norway × Fischer 344, and Fischer 344 × Brown Norway Rats With Relation to Age

text: The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway × Fischer 344 and Fischer 344 × Brown Norway) of rat. Total lesion incidence functions as a biomarker of aging for all of the strains examined (p ≤ .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 × BN F(1) hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.


title: Multidisciplinary approach to evaluating welfare of veal calves in commercial facilities

text: Due to pending legislation and public concerns, a multidisciplinary approach was designed to investigate the welfare of special-fed veal calves in commercial veal facilities. Concerns included housing conditions, dietary regimens, management practices, and behavioral aspects imposed on special-fed calves. Four categories of parameters including environment and housing, nutrition, health and stress, and behavior provided a broad base of evaluating veal systems. Observations and samples were collected on 550 Holstein bull calves located in 10 commercial veal facilities. Each facility was visited to collect data during wk 0 (week of arrival of the calves), 2, 4, 8, 12, and 16. Nine facilities used individual stalls 48 to 55 cm in width with tethers attached to the front of the stalls. One facility housed 30 calves in group pens after obtaining calves at 8 wk of age. Ammonia, carbon monoxide, and hydrogen sulfide gas did not exceed the permissible limit for humans in any facility. All facilities exceeded the 2-foot-candle recommendation for lighting. The average daily gain of calves was .85 kg during wk 0 to 8 and 1.18 kg during wk 8 to 16. Dietary iron levels decreased from 209 ppm at wk 0 to 32 ppm at wk 16. At 16 wk, 25% of calves were marginally anemic and 10% clinically anemic. Overall mortality was 4.2%. Stress indices such as plasma Cortisol concentrations or neutrophil to lymphocyte ratios declined as calves approached market weight. In either pens or stalls, calves spent approximately 25 and 75% of time in standing and lying positions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


title: Interaction of mouse hepatitis virus 3 with Kupffer cells explanted from susceptible and resistant mouse strains. Antiviral activity, interleukin-1 synthesis

text: The genetic sensitivity of mouse strains to mouse hepatitis virus 3 (MHV 3) has been related in vitro to a delay of virus replication in liver sinusoidal cells. In vivo immuno-histochemical studies of the liver from infected mice have demonstrated that mechanisms other than direct viral injury are in operation. To examine potential mechanisms, the interaction of lipopolysaccharide (LPS)-stimulated Kupffer cells with MHV 3 was studied. We first observed a dramatic inhibition in viral replication in LPS-treated Kupffer cells explanted from A/J resistant mice. Second, we demonstrated that MHV 3 induced a dose-dependent interleukin 1 (IL-1) activity in the supernatants of infected Kupffer cells of both strains. These results led us finally to examine the antigen-proceesing function of the Kupffer cellsof both strains of mice. No striking differences were observed in the ability of Kupffer cells from resistant or sensitive mice to collaborate with immunocompetent lymphocytes. Our data suggest that Kupffer cells play a double role which is crucial in the pathogenesis of MHV 3-induced hepatitis. First, they act directly as the genetically determined sensitivity of mice to MHV 3 infection is correlated with the efficiency of the antiviral activity induced in Kupffer cells by LPS. Second, they act indirectly through the synthesis of different amounts of IL-1 induced by MHV 3. This hypothesis is further borne out by the effects of indomethacin treatment on the course of MHV 3 infection in A/J resistant mice in vivo.


title: Zinc Lozenges Reduce the Duration of Common Cold Symptoms

text: A randomized, double‐blind, placebo‐controlled clinical trial has shown that treatment of the common cold with zinc gluconate lozenges resulted in a significant reduction in duration of symptoms of the cold. Patients received zinc‐containing lozenges or placebo lozenges every 2 hours for the duration of cold symptoms. The median time to complete resolution of cold symptoms was 4.4 days in the zinc group compared with 7.6 days in the placebo group. The mechanism of action of zinc in treating the common cold remains unknown.


title: Pathological Characterization of Male Wistar Rats From The Gerontology Research Center

text: Male Wistar rats aged 6–26 months were obtained from the colony of The Gerontology Research Center of the National Institute on Aging, and pathological profiles were assessed. One hundred animals were sacrificed at 6, 12, 18, 21, 24, and 26 months and used for cross-sectional determinations; also, 150 animals were followed longitudinally and sacrificed when clinical signs of moribundity appeared. Renal disease contributed the most common pathology observed in both studies (found in over 70% of the animals examined), with neoplasms a secondary problem (pituitary tumors were by far the most prevalent, with adenomas present in ≈ 20% of the animals). This analysis represents the first complete pathological characterization of this commonly used rat model for aging research, and offers an opportunity for comparison with other rat strains.


title: Nitric oxide in dengue and dengue haemorrhagic fever: necessity or nuisance?

text: Advances in free radical research show that reactive oxygen and nitrogen oxide species, for example superoxide, nitric oxide (NO) and peroxynitrite, play an important role in the pathogenesis of different viral infections, including dengue virus. The pathogenic mechanism of dengue haemorrhagic fever (DHF) is complicated and is not clearly understood. The hallmarks of the dengue disease, the antibody-dependent enhancement, the shift from T-helper type 1 (Th1) to Th2 cytokine response and the cytokine tsunami resulting in vascular leakage can now be explained much better with the knowledge gained about NO and peroxynitrite. This paper makes an effort to present a synthesis of the current opinions to explain the pathogenesis of DHF/shock syndrome with NO on centre stage.


title: Development and evaluation of loop-mediated isothermal amplification (LAMP) for the rapid diagnosis of Penicillium marneffei in archived tissue samples

text: Penicillium marneffei is the etiologic agent of a severe systemic disease in immunocompromised hosts in Southeast Asia. In the present study, a novel method, known as loop-mediated isothermal amplification (LAMP), is described for the rapid and specific detection of the species, using a primer set derived from the internal transcribed spacer (ITS) region of the rRNA gene. Amplification products can be detected macroscopically by visual inspection in vials using SYBR Green I as well as by electrophoresis on agarose gel. The LAMP assay resulted in specific amplification of P. marneffei ITS using pure cultures after a 1-h reaction at 65 °C in a water bath; no cross-reactivity with other fungi including other biverticillate penicillia was observed. The detectable DNA limit was two copies. In addition, specific amplification was achieved using paraffin wax-embedded tissue samples from patients with penicilliosis marneffei and tissue samples from bamboo rats. The method provides a powerful tool for rapid diagnostics in the clinical lab, and has potential for use in ecological studies.


title: Production and characterization of neutralizing monoclonal antibodies that recognize an epitope in domain 2 of Bacillus anthracis protective antigen

text: Antibodies against the protective antigen (PA) of Bacillus anthracis play a key role in response to infection by this important pathogen. The aim of this study was to produce and characterize monoclonal antibodies (mAbs) specific for PA and to identify novel neutralizing epitopes. Three murine mAbs with high specificity and nanomolar affinity for B. anthracis recombinant protective antigen (rPA) were produced and characterized. Western immunoblot analysis, coupled with epitope mapping using overlapping synthetic peptides, revealed that these mAbs recognize a linear epitope within domain 2 of rPA. Neutralization assays demonstrate that these mAbs effectively neutralize lethal toxin in vitro.


Hepatitis A+B Vaccine in Elderly Persons


title: Candidate Biomarkers of Aging: Age-Sensitive Indices of Immune and Muscle Function Covary in Genetically Heterogeneous Mice

text: A longitudinal experiment was designed to test the hypothesis that individual mice differ in their aging rate and to validate candidate biomarkers proposed to measure the rate of aging. Mice were bred as the genetically heterogeneous progeny of a cross between CB6F1 mothers and C3D2F1 fathers. Half of the mice were fed ad libitum (AL group), and the other half were subjected to 60% calorie restriction (CR group). Each mouse was tested at about 9 months of age using age-sensitive tests of immune status, and then again at about 12 months of age using age-sensitive tests of muscle function. The data were then analyzed using the method of partial least squares to determine the combinations of test weights that maximize the covariance of the weighted sum of immune measures with the weighted sum of muscle function measures. Both AL and CR mice exhibited a statistically significant relation between the immune status tests and the muscle function tests. Maximal covariance was obtained with a set of weighting coefficients consistent with our working hypothesis: mice with high levels of CD4 memory T cells (which increase with age) also had relatively low levels of muscle strength and endurance. Low strength was associated with low CD8 cells in the AL mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells in both diet groups. The partial least squares method generates composite indices of immune status and muscle function that can be evaluated as biomarkers of aging rate in these mice. Further work will be needed to assess whether these tests predict either longevity or the trajectory of change in other age-sensitive molecular and physiological traits.


title: Diarrhea: The Nemesis of the Artificially Reared, Early Weaned Piglet and a Strategy for Defense

text: Rearing early weaned piglets artificially for the purposes of increasing the efficiency of the sow is an attractive management concept. However, high death losses resulting from diarrhea in artificially reared piglets have dampered enthusiasm for early weaning. Enterotoxigenic Escherichia coli, transmissible gastroenteritis virus and rotavirus are the three main enteropathogens responsible for causing the diarrhea. The enteropathogens infect the small intestine, which produces a secretory or malabsorptive diarrhea. In nature, the nursing piglet is protected from the enteropathogens by antibody bathing his gut. The source of the antibody is the dam's colostrum and milk. It should be possible to protect artificially reared, early weaned piglets from enteropathogens by feeding them diets that contain antibodies to putative enteropathogens.


The clinical evaluation of antiviral agents. Report of a Working Party of the British Society for Antimicrobial Chemotherapy and the Society of Pharmaceutical Medicine.


title: Oral vaccination of mice against Helicobacter pylori with recombinant Lactococcus lactis expressing urease subunit B

text: To determine whether a protective immune response could be elicited by oral delivery of a recombinant live bacterial vaccine, Helicobacter pylori urease subunit B (UreB) was expressed for extracellular expression in food-grade bacterium Lactococcus lactis. The UreB-producing strains were then administered orally to mice, and the immune response to UreB was examined. Orally vaccinated mice produced a significant UreB-specific serum immunoglobulin G (IgG) response. Specific anti-UreB IgA responses could be detected in the feces of mice immunized with the secreting lactococcal strain. Mice vaccinated orally were significantly protected against gastric Helicobacter infection following a challenge with H. pylori strain SS1. In conclusion, mucosal vaccination with L. lactis expressing UreB produced serum IgG and UreB-specific fecal IgA, and prevented gastric infection with H. pylori.


title: Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

text: Dengue virus universal and serotype 1 to 4 fluorogenic probe hydrolysis, reverse transcription (RT)-polymerase chain reaction (PCR) assays and positive-control RNA template were freeze-dried in a thermally stable, hydrolytic enzyme-resistant format and deployed for testing in a dengue fever-endemic region of Thailand. The study site presented austere testing conditions. Field-collected Aedes aegypti mosquitoes spiked with inoculated A. aegypti mosquitoes and individual and pooled, field-collected, A. aegypti, A. albopictus, and Culex tritaeniorhynchus mosquitoes were used for RT-PCR assay evaluations. For dengue virus-inoculated A. aegypti mosquitoes and spiked samples, in vitro sensitivity and specificity results for all five assays were concordant with indirect fluorescent antibody assay results. A single pool of field-collected, female, A. aegypti mosquitoes was identified as dengue virus positive. Cross-reactivity was not observed across heterologous serotypes, mosquito vectors, or human DNA. The limit of detection was >7 to ≤70 genomic equivalents. Sample processing and analysis required <2 hours. These results show promise of field-formatted RT-PCR reagents for rapid, sensitive, specific dengue virus screening and serotype identification in mosquitoes under field-deployed conditions.


title: Evaluation of New Anti-Infective Drugs for the Treatment of Respiratory Tract Infections

text: These guidelines deal with the evaluation of anti-infective drugs for the treatment of respiratory tract infections. Five clinical entities are described: streptococcal pharyngitis and tonsillitis, otitis media, sinusitis, bronchitis, and pneumonia. A wide variety of microorganisms are potentially pathogenetic in these diseases; these guidelines focus on the bacterial infections. Inclusion of a patient in a trial of a new drug is based on the clinical entity, with the requirement that a reasonable attempt will be made to establish a specific microbial etiology. Microbiologic evaluation of efficacy requires isolation of the pathogen and testing for in vitro susceptibility. Alternatively, surrogate markers may be used to identify the etiologic agent. The efficacy of new drugs is evaluated with reference to anticipated response rates. Establishment of the microbial etiology of respiratory tract infections is hampered by the presence of “normal flora” of the nose, mouth, and pharynx, which may include asymptomatic carriage of potential pathogens. This issue is addressed for each category of infection described. For example, it is suggested that for initial phase 2 trials of acute otitis media and acute sinusitis tympanocentesis or direct sinus puncture be used to collect exudate for culture. Acute exacerbations of chronic bronchitis also present difficulties in the establishment of microbial etiology. These guidelines suggest that clinical trials employ an active control drug but leave open the possibility of a placebo-controlled trial. For pneumonia, the guidelines suggest the identification and enrollment of patients by the clinical type of pneumonia, e.g., atypical pneumonia or acute bacterial pneumonia, rather than by etiologic organism or according to whether it was community or hospital acquired. For each respiratory infection, the clinical response is judged as cure, failure, or indeterminate. Clinical improvement is not acceptable unless quantitative response measures can be applied.


docid: fmdatllr

title: Inheritance and Interaction of Immune Traits in Beef Calves

text: Three sets of blood samples were obtained from beef calves of two experimental populations and assayed for various immunological measurements. The first set of samples was taken between 24 and 48 h after birth and quantified for IgG(1) concentration. A second set was taken immediately prior to vaccination for infectious bovine rhinotracheitis virus (IBRV; at an average age of 164 d) and a third set taken 60 d post-vaccination. These later samples were quantified for antibodies specific to IBRV. Level of complement C3 was also quantified in the samples taken immediately prior to vaccination. Three hundred sixty-seven calves were from four Hereford lines; three lines were previously selected for growth traits and the fourth was a randomly selected control line. There were no consistent differences in immune traits among these lines. The second group of 165 animals were Angus, Hereford and Red Poll calves. While Angus calves had a higher mean IgG(1) concentration at 24 to 48 h of age than Hereford or Red Poll calves, no differences among breeds were found for the other immune traits measured. Calves from older dams (>3 yr old) tended to have higher mean IgG(1) concentrations, pre-vaccination IBRV antibody titers and complement C3 levels than calves from 2- and 3-yr-old cows. However, these calves had lower 60-d post-vaccination IBRV titers than calves from the younger cows (P<.05). As pre-vaccination IBRV antibody titer increased, post-vaccination IBRV antibody titer decreased (P<.05). All pooled heritability estimates did not differ significantly from 0 (range −.06 ± .08 to .21 ± .12), nor were there significant pheno-typic associations between the immune traits and growth performance.


title: Growth, nutrient utilization, and body composition of dairy calves fed milk replacers containing different amounts of protein(1)

text: Male Holstein calves <1 wk of age were allowed a 2-wk adaptation period after purchase, and then were blocked by BW and assigned randomly within block to either a baseline slaughter group or one of four experimental groups (n = 8 to 9 per group). Treatments were isocaloric milk replacers (12.5% solids) fed at 12% of BW that contained 16.1, 18.5, 22.9, or 25.8% CP (DM basis) from whey protein sources. After a 6-wk feeding period, all calves were slaughtered and the weights and chemical composition of the viscera-free carcasses (VFC; including head, hide, feet, and tail) were determined. Gain of BW (0.38, 0.45, 0.56, and 0.62 kg/d) and gain:feed ratio (0.51, 0.59, 0.71, and 0.78) increased linearly (P < 0.001) as dietary CP increased; rate of change in body length, wither height, and heart girth also increased linearly (P ≤ 0.05). Balance measurements conducted during wk 3 and 4 of the experimental period showed that both absorbed N (16.9, 20.0, 25.8, and 30.6 g/d) and retained N (7.6, 9.0, 13.2, and 15.6 g/d) increased linearly (P < 0.001) as dietary CP increased. Retained N as a percentage of absorbed N increased linearly (P < 0.01) as dietary CP increased (44.3, 44.7, 50.7, and 50.9%), whereas biological value was unaffected (71.1, 68.7, 69.5, and 67.3%; P = 0.26). Digestible energy and ME represented 94.5 and 89.7% of intake energy, respectively, and were not affected by dietary CP content. Plasma urea N concentration increased linearly (2.9, 3.3, 4.6, and 6.0 mg/dL) as dietary CP increased. Contents of water (68.2, 69.1, 70.2, and 70.5%; P < 0.001) and protein (19.6, 20.0, 20.0, and 20.2%; P < 0.10) in VFC increased linearly, whereas contents of fat (7.2, 6.2, 5.5, and 5.2%; P < 0.001) and ash (5.1, 5.2, 4.8, and 4.7%; P < 0.02) decreased linearly as dietary CP increased. Trends in visceral tissue composition were similar to those for VFC. The content of water in VFC tissue gain increased, whereas contents of fat and energy decreased, as dietary CP increased. Final VFC energy and gain of energy in VFC were not affected by dietary CP. At similar initial ME intakes, increasing dietary CP (i.e., increasing protein:energy) linearly increased ADG, gain:feed, N retention, and deposition of lean tissue in VFC, demonstrating that diet composition can markedly affect components of body growth in preruminant dairy calves.


title: Mammary expression of new genes to combat mastitis

text: Continual advances in the ability to produce transgenic animals make it likely that such animals will become important components of animal agriculture. The full benefit of the technology, and justification of its initial cost outlay, will be dependent on the establishment within these animals of new traits not easily achievable by other means. Potential applications include enhanced nutrient digestibility with reduced fecal losses, significantly altered milk composition with superior nutritional properties, and enhanced disease resistance. Our goal is to enhance mastitis resistance of dairy cows by enabling the cells of the mammary gland to secrete additional antibacterial proteins. Proof of concept has been obtained through experimentation with a transgenic mouse model. Three lines of mice were developed that produce varying levels of lysostaphin in their milk. This protein has potent anti-staphylococcal activity and its secretion into milk confers substantial resistance to infection caused by intramammary challenge with Staphylococcus aureus, a major mastitis pathogen. Additional antibacterial proteins are being sought that will complement lysostaphin. A potential benefit of transgenic application of antibacterial proteins is the concomitant sparing in the agricultural use of antibiotics currently used as human therapeutics. Antibacterial proteins, such as lysostaphin, are not typically used as injectable or oral therapeutics because of immune-mediated or digestive destruction of their activity. In contrast, the immune system of transgenic animals will not consider the transgenic protein as being foreign. In addition we are exploring the potential of involution or mastitis responsive promoter elements for use in subsequent transgenic experiments designed to restrict lysostaphin production to these important time points. It is anticipated that genomics will play a role in unveiling candidate genes whose promoter elements will enable desired temporal expression patterns. The transgenic approach to insertion of new genetic material into agriculturally important animals is feasible but requires extensive prior evaluation of the transgene and transgene product in model systems.


title: CNS Manifestations Associated with Mycoplasma pneumoniae Infections: Summary of Cases at the University of Helsinki and Review

text: CNS manifestations appear in one of 1,000 patients with Mycoplasma pneumoniae-associated infections. Encephalitis is the most frequent manifestation, but cases of meningitis, myelitis, and polyradiculitis, as well as many other symptoms (e.g., coma, ataxia, psychosis, and stroke), have been reported. The onset of these manifestations is usually acute, with lowered consciousness, convulsions, pareses, and other neurological signs. Severe, even fatal, cases are known. The pathophysiology of CNS manifestations is unknown. To our knowledge, M. pneumoniae has never been isolated from brain tissue, but instead it has been recovered from CSF specimens in at least seven cases. Besides direct invasion of M. pneumoniae into the brain, neurotoxic or autoimmune reaction within the brain tissue is suspected. At neuropathological examination, edema, demyelination, and microthrombi have been described. Improved diagnostic methods may reveal the pathophysiology of CNS manifestations associated with M. pneumoniae infection.


title: A Perspective from Controlled Investigations on Chemotherapy for Viral Respiratory Infections

text: Failure to translate discoveries about the etiology of viral respiratory infections into effective vaccines has stimulated research into antiviral chemotherapy. Volunteers whose antibody status before challenge is known and who have been exposed to a known dose of virus at a defined time provide an objective system for controlled observation of antiviral chemotherapy. A perspective on experience with drugs of five different categories of mechanisms of action is presented. Prophylactic and possibly therapeutic control of influenza and rhinovirus infections is possible. Field trials have confirmed that some regimens have beneficial effects and have shown the clinical restrictions of others. Chemotherapy is enhanced by immunoprophylaxis, and vice versa. If the potential of antiviral chemotherapy for clinical use is to be realized, complex virologic problems (some related to drugs and others unrelated) must be overcome. The groundwork is laid for new directions and new successes in the prevention and treatment of viral respiratory diseases with antiviral drugs.


Parallel Session 27 – Sickness Absence


title: Age-Sensitive T Cell Phenotypes Covary in Genetically Heterogeneous Mice and Predict Early Death From Lymphoma

text: We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44(hi)) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RB(hi)) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels ofCD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to con a and 1l-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases offollicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages. Since each of the prognostic immune indices is characteristically seen in aged mice, we suggest that relatively precocious aging of the immune system may predispose a mouse to early death, particularly from lymphoma


docid: epchoupz

title: Dengue in infants: an overview

text: Dengue virus (DV) infection causes either a benign syndrome, dengue fever, or a severe syndrome, dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS), that is characterized by systemic capillary leakage, thrombocytopaenia and hypovolaemic shock. DHF/DSS occur mainly due to secondary infection by a heterotype DV infection in children and adults but in infants even primary infection by DV causes DHF/DSS. Clinical manifestations of DHF/DSS are more significantly associated with death in infants compared with older children. Vertical transmission of DV and anti-DV IgG has been well reported and is responsible for the pathogenesis of DV disease and its manifestations in infants. The complex pathogenesis of DHF/DSS during primary dengue in infants, with multiple age-related confounding factors, offers unique challenges to investigators. Dengue in infants is not often studied in detail due to practical limitations, but looking at the magnitude of DHF/DSS in infants and the unique opportunities this model provides, there is a need to focus on this problem. This paper reviews existing knowledge on this aspect of DV infection and the challenges it provides.


title: Therapeutics in Ferrets

text: The domestic ferret (Mustela putorius furo) continues to grow in popularity as a pet species in North America as well as many countries around the world. With this rapid growth comes an increased potential for small and exotic animal practitioners to expand their ferret clientele. This article reviews the commonly used therapeutics in ferrets, as well as the general principles and guidelines for their use.


docid: wccmeaep

title: Emergency and Critical Care of Ferrets

text: Ferrets are becoming increasingly popular as pets in the United States. Emergency situations involving ferrets are most often caused by gastrointestinal disease, neoplasia, cardiac disease, or endocrinopathy. Hospitalization and supportive care of the critically ill ferret, emergency treatment techniques, and diagnostic procedures are discussed. Diseases most commonly involved in critical presentations are reviewed along with treatment protocols.


title: Highly conserved M2e and hemagglutinin epitope-based recombinant proteins induce protection against influenza virus infection

text: Highly pathogenic influenza viruses continue to cause serious threat to public health due to their pandemic potential, calling for an urgent need to develop effective, safe, convenient, and universal vaccines against influenza virus infection. In this study, we constructed two recombinant protein vaccines, 2H5M2e-2H7M2e-H5FP-H7FP (hereinafter M2e-FP-1) and 2H5M2e-H5FP-2H7M2e-H7FP (hereinafter M2e-FP-2), by respectively linking highly conserved sequences of two molecules of ectodomain of M2 (M2e) and one molecule of fusion peptide (FP) epitope of hemagglutinin (HA) of H5N1 and H7N9 influenza viruses in different orders. The Escherichia coli-expressed M2e-FP-1 and M2e-FP-2 proteins induced similarly high-titer M2e-FP-specific antibodies in the immunized mice. Importantly, both proteins were able to prevent lethal challenge of heterologous H1N1 influenza virus, with significantly reduced viral titers and alleviated pathological changes in the lungs, as well as increased body weight and complete survivals, in the challenge mice. Taken together, our study demonstrates that highly conserved M2e and FP epitope of HA of H5N1 and H7N9 influenza viruses can be used as important targets for development of safe and economical universal influenza vaccines, and that the position of H7N9 M2e and H5N1 HA epitope sequences in the vaccine components has no significant effects on the immunogenicity and efficacy of M2e-FP-based subunit vaccines.


SARS & the Health Care System: Exploring Your Questions About This New Infectious Disease


title: What Role Is There for Antithymocyte Globulin in Allogeneic Nonmyeloablative Canine Hematopoietic Cell Transplantation?

text: We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit engraftment of canine dog leukocyte antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum levels of ATG peaked on days 4 to 6 after initiation of therapy and became undetectable by day 13 as a result of canine antibody responses to ATG. ATG prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days in control dogs (P = .0003). Five dogs were given marrow transplants after ATG (3.5–5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained engraftment, and 4 rejected their grafts. The duration of engraftment ranged from 8 to ≥36 weeks (median, 11 weeks), and this is comparable to that in 6 historical controls not given ATG (range, 3–12 weeks; median, 10 weeks; P = .20). The total nucleated cell doses in the marrow grafts had the highest correlation coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI failed to secure uniform stable hematopoietic engraftment.


title: Passerine and Softbill Therapeutics

text: Passerines (songbirds) and softbills (toucans and mynahs) are increasingly presented for veterinary care as pet owners and aviculturists recognize that successful medical and surgical treatment can be performed in these often tiny patients. Even with an increasing amount of pharmacokinetic data in birds, the use of extrapolated drug regimens continues to be a common practice for these species. The extrapolation, using allometric scaling from human, mammalian, and avian drugs to passeriformes and softbills, is complicated and limited. In this article, the choice of the therapeutic approach is discussed. Once the choice for a specific drug is made, tables help calculate the dose in milligrams per kilocalorie without using complicated formulas.


Patient Safety Tools: SARS, Smallpox, Monkeypox, and Avian Flu


A propósito de un caso de neumonía redonda


Abstracts from the 25th Italian Congress of Cystic Fibrosis and the 15th National Congress of Cystic Fibrosis Italian Society: Assago, Milan. 10 - 12 October 2019


title: Oncology nurses’ compassion fatigue, burn out and compassion satisfaction

text: BACKGROUND: For oncology nurses, compassion fatigue, burn out and compassion satisfactions are frequently experienced psychosocial consequences of the oncology work environment. Surveying such phenomena helps to understand how nurses feel and behave when cancer care is provided. Besides, tracking the evolving nature of those three concepts can lend a hand for the early detection of personal and professional suffering of nurses while offering some healing remedies to their struggling bodies and souls. PURPOSE: The purpose of this study was to explore the level of compassion fatigue, burn out and compassion satisfaction among a group of specialized oncology nurses. Besides, this study aimed to detect some probable interesting inferences between compassion satisfaction and the concept of rest and leisure. Correlations between compassion fatigue, burn out and compassion satisfaction were investigated. Correlations between oncology nurses’ scores on the three subscales and a group of demographic, organizational and leisure-related variables were examined. METHODS: This study adopted a descriptive correlation design to survey compassion fatigue, burn out and compassion satisfaction among a convenient sample of 100 oncology nurses who work in a specialized cancer care centre. Participants completed compassion fatigue self-test developed by Figely (Compassion fatigue, New York: Brunner/Mazel. B. HudnallStamm, Traumatic Stress Research Group; 1995–1998. http://www.dartmouth.edu/~bhstamm/index.htm, 1995) and a literature-based demographic survey. Analysis of data included descriptive statistics and Pearson correlation co-efficient. RESULTS: Nurses reported a low level of compassion satisfaction, moderate risk for burn out and an extremely high risk for compassion fatigue. Results revealed significant negative relationships among compassion satisfaction and the number of dependents per nurse. Additionally the correlation between compassion satisfaction and the nurses’ number of hours slept was positive. Only two components of the concept rest and leisure yielded statistical significance when correlated to the concept of compassion satisfaction. A significant negative relationship was observed between compassion satisfaction and compassion fatigue while a strong positive relationship was observed between compassion fatigue and burn out. CONCLUSIONS: The studied oncology nurses sample had evidently low level of compassion satisfaction when contrasted to the significantly increased risks of burn out and compassion fatigue. Thus, health authorities and management are advised to care, in a holistic approach, for nurses who work in oncology departments. Staff-oriented services that offer comfort, reward, leisure, screening, consultation and support are urgently recommended.


title: Clinical Pathology and Sample Collection in the Laboratory Rodent

text: Common laboratory rodents have always been a favorite choice as a pet. Although diagnostic clinical pathology has not been viewed as practical for the rodent patient, current advances in technology make processing of small samples possible. Cultivation of the technical skills necessary for rodent sample collection has the potential to improve the standard of rodent veterinary care. This article provides an overview of rodent sample collection techniques, hematology, clinical biochemistry, serology, and clinical pathology of other tissues and fluids for laboratory rodents. General principles of clinical pathology can be applied across species. This article emphasizes the subtleties of the different rodent species which may impact diagnostic interpretation.


title: Development of a State Medical Surge Plan, Part II: Components of a Medical Surge Plan

text: In 2003, the Utah State Department of Health received funding from the Health Resources and Services Administration to develop a medical surge plan to increase the number of available hospital beds in the state by 1250 beds, including 125 beds for burn or critical trauma patients. A prior article discussed the planning procedures and process. This article describes the major components of the plan, including analysis of threats, direction and control, activation and system response; communications; and critical issues.


title: Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

text: BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO(2) > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO(2) ≥ 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO(2) < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO(2) use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO(2) use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO(2). Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO(2) use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO(2) use, compared to 39% in a propensity-matched sample of normoxemic (PaO(2) 55–100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073


title: Viral metagenomics and blood safety

text: The characterization of the human blood-associated viral community (also called blood virome) is essential for epidemiological surveillance and to anticipate new potential threats for blood transfusion safety. Currently, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) can be considered as under control in high-resource countries. However, other viruses unknown or unsuspected may be transmitted to recipients by blood-derived products. This is particularly relevant considering that a significant proportion of transfused patients are immunocompromised and more frequently subjected to fatal outcomes. Several measures to prevent transfusion transmission of unknown viruses have been implemented including the exclusion of at-risk donors, leukocyte reduction of donor blood, and physicochemical treatment of the different blood components. However, up to now there is no universal method for pathogen inactivation, which would be applicable for all types of blood components and, equally effective for all viral families. In addition, among available inactivation procedures of viral genomes, some of them are recognized to be less effective on non-enveloped viruses, and inadequate to inactivate higher viral titers in plasma pools or derivatives. Given this, there is the need to implement new methodologies for the discovery of unknown viruses that may affect blood transfusion. Viral metagenomics combined with High Throughput Sequencing appears as a promising approach for the identification and global surveillance of new and/or unexpected viruses that could impair blood transfusion safety.


Climate change and multiple emerging infectious diseases()


title: Influences of degree inhomogeneity on average path length and random walks in disassortative scale-free networks

text: Various real-life networks exhibit degree correlations and heterogeneous structure, with the latter being characterized by power-law degree distribution [Formula: see text] , where the degree exponent [Formula: see text] describes the extent of heterogeneity. In this paper, we study analytically the average path length (APL) of and random walks (RWs) on a family of deterministic networks, recursive scale-free trees (RSFTs), with negative degree correlations and various [Formula: see text] , with an aim to explore the impacts of structure heterogeneity on the APL and RWs. We show that the degree exponent [Formula: see text] has no effect on the APL [Formula: see text] of RSFTs: In the full range of [Formula: see text] , [Formula: see text] behaves as a logarithmic scaling with the number of network nodes [Formula: see text] (i.e., [Formula: see text]), which is in sharp contrast to the well-known double logarithmic scaling [Formula: see text] previously obtained for uncorrelated scale-free networks with [Formula: see text]. In addition, we present that some scaling efficiency exponents of random walks are reliant on the degree exponent [Formula: see text].


title: Computational model of a vector-mediated epidemic

text: We discuss a lattice model of vector-mediated transmission of a disease to illustrate how simulations can be applied in epidemiology. The population consists of two species, human hosts and vectors, which contract the disease from one another. Hosts are sedentary, while vectors (mosquitoes) diffuse in space. Examples of such diseases are malaria, dengue fever, and Pierce's disease in vineyards. The model exhibits a phase transition between an absorbing (infection free) phase and an active one as parameters such as infection rates and vector density are varied.