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One subject of spatial epidemiology is spatial variation in disease risk or incidence. The spread of epidemics can result in strong spatial patterns of such risk or incidence: for example, pathogen dispersal might be highly localized, vectors or reservoirs for pathogens might be spatially restricted, or susceptible hosts might be clumped. Here, spatial pattern of an epidemic model with nonlinear incidence rates is investigated. The conditions for Hopf bifurcation and Turing bifurcation are gained and, in particular, exact Turing domain is found in the two parameters space. Furthermore, numerical results show that force of infection, namely β, plays an important role in the spatial pattern. More specifically, different patterns emerge as β increases. The mathematical analysis and numerical results well extend the finding of pattern formation in the epidemic models and may well explain the field observed in some areas. |
Lower urinary tract infections (UTIs) are common among the general population and are most often caused by bacterial pathogens. Viruses are an uncommon cause of UTIs in an immunocompetent host; however, viruses are increasingly recognized as the cause of lower UTI, especially hemorrhagic cystitis, among immunocompromised patients. BK virus, adenovirus, and cytomegalovirus are predominant pathogens involved in hemorrhagic cystitis after stem cell and solid organ transplantation, and their early diagnosis and treatment may prevent significant morbidity of hemorrhagic cystitis. The diagnosis of viral lower UTI is based on molecular techniques, and real-time polymerase chain reaction is often the method of choice because it allows for quantification of viral load. Cidofovir is becoming a drug of choice in viral UTIs because it is active against the most common viral pathogens. This review discusses the epidemiology, pitfalls in diagnosis, and current treatment of viral UTIs. |
We find that the novel A/H1N1 influenza viruses exhibit very low genetic divergence and suffer strong purifying selection among human population and confirm that they originated from the reassortment of previous triple-reassortant swine influenza viruses including genomic segments from both avian and human lineages with North American and Eurasian swine lineages. The longer phylogenetic branch length to their nearest genetic neighbors indicates that the origin of the novel A/H1N1 is unlikely to be a very recent event. Seventy-six new unique mutations are found to be monomorphically fixed in the novel A/H1N1 virus lineages, suggesting a role of selective sweep in the early evolution of this virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-009-0393-7) contains supplementary material, which is available to authorized users. |
Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed. |
A prospective study was conducted from November 2013 to February 2014 to estimate the spatial clustering; cumulative incidence and risk factors associated with avian influenza (AI) subtype H9 infection on commercial poultry farms of Pakistan. A total of 400 farms were enrolled and followed during the study period. Among these, 109 farms submitted samples suspected for AI to the laboratory, and only 47 farms were confirmed positive by hemagglutinin inhibition (HI) test. Data was collected from these 109 farms about their demography, management, and biosecurity practices. The cumulative incidence of H9N2 was 11.75 % (95 % confidence interval (CI) 8.76–15.23). The highest number of cases (40.42 %) was reported in January. One most likely cluster (p = 0.009, radius = 4.61 km) occurred in the Kasur district. Multivariable logistic regression analyses showed that the presence of wild birds on the farms (odds ratio (OR) = 16.18; 95 % CI 3.94–66.45) was independently associated with H9N2 infection. Cleaning of cages before delivery on farm (OR = 0.16; 95 % CI = 0.06–0.47), presence of a footbath at the entrance of farm (OR = 0.24; 95 % CI 0.08–0.79), and changing of gloves (OR = 0.33; 95 % CI 0.11–0.99) were protective factors against H9N2 infection. Reducing the exposure to risk factors and adapting biosecurity measures may reduce the risk of AI H9N2 infection on commercial poultry farms in Pakistan. |
Two or three regions containing three or more successive newly defined heptads of a–d hydrophobic amino acid repeats have been located in the cDNA-derived amino acid sequences of glycoprotein G of all rhabdoviruses examined (rabies, vesicular stomatitis, fish, and plant rhabdoviruses) by computer search. These new heptad-repeats differ from those previously reported in other viruses because of the presence of all the hydrophobic amino acids in positions a or d, and because they are not predicted to form coiled coils by current methods and thus they have not been detected previously in any rhabdoviruses. The two or three heptad-repeat regions were the only parts of the glycoprotein with at least three successive heptad-repeats in all the rhabdoviral sequences studied and had low sequence variability among the members of each of the rhabdoviral genus but show no sequence similarity among the different genus. All these newly detected heptad repeats were in the vicinity of some of the higher hydrophobic regions in each of the rhabdovirus genera studied and were found mostly, but not always, outside the extra amino acid sequences that occur in the longer insect or plant rhabdovirus glycoprotein G. The correspondence of position and structure of these heptad-repeats among all the rhabdoviruses suggests its participation in common function(s), most probably related to viral fusion with cellular membranes. |
The toxicity and low success of current treatments for Leishmaniosis determines the search of new peptide drugs and/or molecular targets in Leishmania pathogen species (L. infantum and L. major). For example, Ribonucleases (RNases) are enzymes relevant to several biologic processes; then, theoretical and experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs) of RNases is useful for drug design. This study introduces a methodology that combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We illustrate this approach by investigating for the first time the PMFs of a new protein of L. infantum. Here we report and compare new versus old predictive models for RNases based on Topological Indices (TIs) of Markov Pseudo-Folding Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include: Spectral moments π (k)(x,y), Mean Electrostatic potentials ξ (k)(x,y), and Entropy measures θ (k)(x,y). The accuracy of the models (training/cross-validation) was as follows: ξ (k)(x,y)-model (96.0%/91.7%)>π (k)(x,y)-model (84.7/83.3) > θ (k)(x,y)-model (66.0/66.7). We also carried out a 2D-E analysis of biological samples of L. infantum promastigotes focusing on a 2D-E gel spot of one unknown protein with M<20, 100 and pI <7. MASCOT search identified 20 proteins with Mowse score >30, but not one >52 (threshold value), the higher value of 42 was for a probable DNA-directed RNA polymerase. However, we determined experimentally the sequence of more than 140 peptides. We used QSAR models to predict RNase scores for these peptides and BLAST alignment to confirm some results. We also calculated 3D-folding TIs based on MD experiments and compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular diversity of these peptides. This combined strategy may be of interest in drug development or target identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11030-009-9178-0) contains supplementary material, which is available to authorized users. |
Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin’s potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community. |
A nondisposable, or “hard”, multiwell microplate is described for use with small volumes of biological solutions containing organic solvents. The design of this teflon-coated, aluminum device resembles the 96-well layout of the disposable variety of tissue culture microplates. The reusable, hard microplate has been specifically developed to hold and evaporate volatile organic solvents from aliquots of crude sample extractions or partitions intended for testing in various in vitro biological screening assays. This device is a valuable adjunct for converting numerous small volumes of nonpolar or nonaqueous dissolved compounds into reconstituted solutions containing acceptable assay solvents. |
OBJECTIVE: To determine whether antibiotic and bronchodilator treatment of acute bronchitis in patients without lung disease is efficacious. DESIGN: A MEDLINE search of the literature from 1966 to 1995 was done, using “Bronchitis” as the key word. Papers addressing acute bronchitis in adults were used as well as several citations emphasizing pediatric infections. A manual search of papers addressing the microorganisms causing acute bronchitis was also done. Data were extracted manually from relevant publications. SETTING: All published reports were reviewed. Papers dealing with exacerbations of chronic bronchitis were excluded in this review. RESULTS: Although acute bronchitis has multiple causes, the large majority of cases are of viral etiology.Mycoplasma pneumoniae, Chlamydia pneumoniae, andBordetella pertussis are the only bacteria identified as contributing to the cause of acute bronchitis in otherwise healthy adults. Nine double-blind, placebo-controlled trials were reviewed. Four studies showed no advantage for doxycycline and one study showed no advantage for erythromycin. One study using erythromycin and one study using trimethoprim and sulfamethoxazole showed that these antibiotics were slightly better than placebo. Two other studies showed an impressive superiority for liquid or inhaled albuterol when compared with erythromycin. CONCLUSIONS: Most studies showed no significant difference between drug and placebo, and the two studies that did showed only small clinical differences. Albuterol had an impressive advantage over erythromycin. Antibiotics should not be used in the treatment of acute bronchitis in healthy persons unless convincing evidence of a bacterial infection is present. |
This paper discusses the application of the supreme emergency doctrine from just-war theory to non-antagonistic threats. Two versions of the doctrine are considered: Michael Walzer’s communitarian version and Brian Orend’s prudential one. I investigate first whether the doctrines are applicable to non-antagonistic threats, and second whether they are defensible. I argue that a version of Walzer’s doctrine seems to be applicable to non-antagonistic threats, but that it is very doubtful whether the doctrine is defensible. I also argue that Orend’s version of the doctrine is applicable to non-antagonistic threats, but that his account is not defensible, regardless of whether the threats are antagonistic or not. |
Herpes simplex virus type 2 (HSV-2) is the major cause of genital herpes in humans. The glycoprotein D of HSV-2 (gD2) is a promising subunit vaccine candidate for the treatment of genital herpes. The aim of the present study was to express a biologically active recombinant gD2 in eukaryotic baculovirus system in quantities sufficient for further studies. Human cDNA encoding a gD2 protein with 393 amino acids was subcloned into the pFastBac HTb vector and the recombinant protein was expressed in Spodoptera frugiperda (Sf9) cells by high-density cell culture. In a stirred bioreactor, the key limiting factors including glucose concentration, glutamine concentration and dissolved oxygen (DO) were optimized for high-density cell growth. The Sf9 cell density could reach 9.6×10(6) cells/mL and the yield of recombinant gD2 protein was up to 192 mg/L in cell culture under the optimal conditions of 15 mM glucose, 0.4 g/L glutamine and 40% DO. Production of significant amounts of pure, full-length gD2 opened up the possibility to investigate novel functions of gD2. Moreover, the purified recombinant gD2 protein revealed a partial prophylactic immune function in genital herpes of guinea pigs infected with HSV-2. |
The results of detection and identification of Bacillus anthracis strains in loop-mediated isothermal DNA amplification (LAMP) reaction performed under optimized conditions with original primers and thermostable DNA polymerase are presented. Reproducible LAMP-based detection of chromosomal and plasmid DNA targets specific for B. anthracis strains has been demonstrated. No cross reactions with DNA from bacterial strains of other species of the B. cereus group were detected. The development of tests for anthrax-pathogen detection based on the optimized reaction of loop isothermal DNA amplification is planned. These tests will be convenient for clinical studies and field diagnostics due to the absence of requirements for sophisticated equipment. |
The genomic RNA of hepatitis C virus (HCV) encodes the viral polyprotein precursor that undergoes proteolytic cleavage into structural and nonstructural proteins by cellular and the viral NS3 and NS2-3 proteases. Nonstructural protein 4A (NS4A) is a cofactor of the NS3 serine protease and has been demonstrated to inhibit protein synthesis. In this study, GST pull-down assay was performed to examine potential cellular factors that interact with the NS4A protein and are involved in the pathogenesis of HCV. A trypsin digestion followed by LC-MS/MS analysis revealed that one of the GST-NS4A-interacting proteins to be eukaryotic elongation factor 1A (eEF1A). Both the N-terminal domain of NS4A from amino acid residues 1–20, and the central domain from residues 21–34 interacted with eEF1A, but the central domain was the key player involved in the NS4A-mediated translation inhibition. NS4A(21–34) diminished both cap-dependent and HCV IRES-mediated translation in a dose-dependent manner. The translation inhibitory effect of NS4A(21–34) was relieved by the addition of purified recombinant eEF1A in an in vitro translation system. Taken together, NS4A inhibits host and viral translation through interacting with eEF1A, implying a possible mechanism by which NS4A is involved in the pathogenesis and chronic infection of HCV. |
There is a widespread consensus that the earth is experiencing a mass extinction event and at the forefront are amphibians, the most threatened of all vertebrate taxa. A recent assessment found that nearly one-third (32%, 1,856 species) of the world’s amphibian species are threatened. Amphibians have existed on the earth for over 300 million years, yet in just the last two decades there have been an alarming number of extinctions, nearly 168 species are believed to have gone extinct and at least 2,469 (43%) more have populations that are declining. Infectious diseases have been recognized as one major cause of worldwide amphibian population declines. This could be the result of the appearance of novel pathogens, or it could be that exposure to environmental stressors is increasing the susceptibility of amphibians to opportunistic pathogens. Here I review the potential effects of stressors on disease susceptibility in amphibians and relate this to disease emergence in human and other wildlife populations. I will present a series of case studies that illustrate the role of stress in disease outbreaks that have resulted in amphibian declines. First, I will examine how elevated sea-surface temperatures in the tropical Pacific since the mid-1970s have affected climate over much of the world and could be setting the stage for pathogen-mediated amphibian declines in many regions. Finally, I will discuss how the apparently rapid increase in the prevalence of amphibian limb deformities is linked to the synergistic effects of trematode infection and exposure to chemical contaminants. |
In some situations, a decision is best represented by an incompletely analyzed act: conditionally on a given event A, the consequences of the decision on sub-events are perfectly known and uncertainty becomes probabilizable, whereas the plausibility of this event itself remains vague and the decision outcome on the complementary event [Formula: see text] is imprecisely known. In this framework, we study an axiomatic decision model and prove a representation theorem. Resulting decision criteria aggregate partial evaluations consisting of (i) the conditional expected utility associated with the analyzed part of the decision, and (ii) the best and worst consequences of its non-analyzed part. The representation theorem is consistent with a wide variety of decision criteria, which allows for expressing various degrees of knowledge on ([Formula: see text]) and various types of attitude toward ambiguity and uncertainty. This diversity is taken into account by specific models already existing in the literature. We exploit this fact and propose some particular forms of our model incorporating these models as sub-models and moreover expressing various types of beliefs concerning the relative plausibility of the analyzed and the non-analyzed events ranging from probabilities to complete ignorance that include capacities. |
Sera from five traditionally managed herds grazing in the Kafue flats were tested for antibodies to bovine viral diarrhoea-mucosal disease (BVD-MD), parainfluenza 3 (PI3), infectious bovine rhinotracheitis-infectious pustular vulvovaginitis (IBR-IPV), bovine adenovirus 3 (BAV3) and Bluetongue (BT). The sero-prevalences of the first four diseases were respectively 76.2, 94.4, 42.1 and 87.4%. Five samples (2.3%) gave doubtful reactions for BT. Prevalences of 28.5% for brucellosis, 14% for Rift Valley fever (RFV), 0.9% for Q fever and 11.2% for chlamydiosis were also recorded. Significantly higher values for BVD-MD (p<0.005), IBR-IPV (p<0.01) and brucellosis (p<0.05) were found in animals over 1 year of age. No differences were recorded between herds or between male and female animals. The high concentration of wild and domestic ruminants grazing together in the flood plains during the dry season may be a major determinant of the high values observed. Traditional farmers, slaughterhouse workers and other people involved in livestock production are particularly at risk of contracting brucellosis and RVF because of the high prevalences in cattle and local habits favourable to their transmission. |
Three lines of observation demonstrate the role of arthropods in transmission and evolution of viruses. a) Recent outbreaks of viruses from their niches took place and insects have played a major role in propagating the viruses. b) Examination of the list of viral families and their hosts shows that many infect invertebrates (I) and vertebrates (V) or (I) and plants (P) or all kingdoms (VIPs). This notion holds true irrespective of the genome type. At first glance the argument seems to be weak in the case of enveloped and non-enveloped RNA viruses with single-stranded (ss) segmented or non-segmented genomes of positive (+) or negative polarity. Here, there are several families infecting V or P only; no systematic relation to arthropods is found. c) In the non-enveloped plant viruses with ss RNA genomes there is a strong tendency for segmentation and individual packaging of the genome pieces. This is in contrast to ss+ RNA animal viruses and can only be explained by massive transmission by seed or insects or both, because individual packaging necessitates a multihit infection. Comparisons demonstrate relationships in the nonstructural proteins of double-stranded and ss+ RNA viruses irrespective of host range, segmentation, and envelope. Similar conclusions apply for the negative-stranded RNA viruses. Thus, viral supergroups can be created that infect V or P and exploit arthropods for infection or transmission or both. Examples of such relationships and explanations for viral evolution are reviewed and the arthropod orders important for cell culture are given. |
With the consideration of mechanism of prevention and control for the spread of viral diseases, in this paper, we propose two novel virus dynamics models where state feedback control strategies are introduced. The first model incorporates the density of infected cells (or free virus) as control threshold value; we analytically show the existence and orbit stability of positive periodic solution. Theoretical results imply that the density of infected cells (or free virus) can be controlled within an adequate level. The other model determines the control strategies by monitoring the density of uninfected cells when it reaches a risk threshold value. We analytically prove the existence and orbit stability of semi-trivial periodic solution, which show that the viral disease dies out. Numerical simulations are carried out to illustrate the main results. |
Experimental data are provided for the presence of a plant protein that interacts with the capsid protein (CP) of turnip mosaic potyvirus (TuMV). The receptor-like protein was identified by exploiting the molecular mimicry potential of anti-idiotypic antibodies. A single-chain Fv molecule derived from the monoclonal antibody 7A (Mab-7A), which recognizes the CP of TuMV, was produced in Escherichia coli and the recombinant protein was used to raise rabbit antibodies. The immune serum reacted with Mab-7A but not with a monoclonal antibody of the same isotype, indicating that anti-idiotypic antibodies were produced. These anti-idiotypic antibodies recognized a 37 kDa protein from Lactuca sativa. Complex formation between the anti-idiotypic antibodies and the plant protein was inhibited by the CP of TuMV which indicates that the plant protein interacts with the viral protein. The 37 kDa protein was localized in chloroplasts and was detected in other plant species. |
Although edible vaccines seem to be feasible, antigens of human pathogens have mostly been expressed in plants that are not attractive for human consumption (such as potatoes) unless they are cooked. Boiling may reduce the immunogenicity of many antigens. More recently, the technology to transform fruit and vegetable plants have become perfected. We transformed carrot plants with Agrobacterium tumefaciens to generate plants (which can be eaten raw) transgenic for an immunodominant antigen of the measles virus, a major pathogen in man. The hemagglutinin (H) glycoprotein is the principle target of neutralizing and protective antibodies against measles. Copy numbers of the H transgene were verified by Southern blot and specific transcription was confirmed by RT-PCR. The H protein was detected by western blot in the membrane fraction of transformed carrot plants. The recombinant protein seemed to have a 8% lower molecular weight than the viral protein. Although this suggests a different glycosylation pattern, proper folding of the transgenic protein was confirmed by conformational-dependent monoclonal antibodies. Immunization of mice with leaf or root extracts induced high titres of IgG1 and IgG2a antibodies that cross-reacted strongly with the measles virus and neutralized the virus in vitro. These results demonstrate that transgenic carrot plants can be used as an efficient expression system to produce highly immunogenic viral antigens. Our study may pave the way towards an edible vaccine against measles which could be complementary to the current live-attenuated vaccine. |
Part of the dorsal funiculus of the adult male rat (Wistar) spinal cord was treated for l h at the thoracolumbar level by running hot water, at approximately 48–50 ° C, through a polyethylene tube 2 mm in diameter in contact with the dura. Animals were fixed 1 day to 4 weeks later and the spinal cords were examined by light and electron microscopy. The affected area in the dorsal funiculus was approximately 1 mm long and less than 1 mm wide at the dorsal surface, and varied from 0.4 to 0.7 mm in depth. Within 3 days after treatment, almost all the myelin sheaths in the affected area were degraded, leaving the axons denuded, and at the same time astrocyte endfeet at the glial limiting membrane were swollen and partly destroyed. Almost all the denuded axons remained intact, exhibiting no noticeable morphological changes. There was evidence of a moderate vasogenic oedema, but minimal signs of haemorrhage in the lesion. Seven days after treatment, many immature Schwann cells but no oligodendrocytes were found between the denuded axons. By 2 weeks many of the denuded axons were remyelinated, and by 4 weeks almost all of those axons located near the pial and perivascular surfaces had been remyelinated by Schwann cells, while most of those located in the deep and marginal zones bordering the adjoining intact areas were remyelinated by oligodendrocytes. Longitudinal sections revealed that at nodes of Ranvier PNS-type myelin sheaths were apposed by either intact or newly formed CNS-type myelin sheaths. A typical glial limiting membrane was not reformed beneath the pial surface, but an inconspicuous one was found between the PNS- and CNS-type fibre areas. |
Classical methods for detection of Chlamydophila species, and of antibodies against these agents, have indicated that these bacteria are highly prevalent in cattle and associated with numerous disease conditions. These methods demonstrated acute Chlamydophila-induced diseases such as epizootic bovine abortion, as well as worldwide variable, but generally high, Chlamydophila seroprevalence. However, it was impossible to consistently detect the low levels of these organisms which were suspected to be present in endemic infections. Application of highly sensitive real-time PCR and ELISA methods for detection of Chlamydophila spp. DNA and of antibodies against Chlamydophila spp., respectively, in a series of prospective cohort studies revealed a high prevalence of Chlamydophila spp. genital infections in female calves (61%) and adult heifers (53%). These infections were acquired by extragenital transmission in the first weeks of life, and infection frequency was increased by crowding of the animals. A challenge study demonstrated that infection with C. abortus resulted in decreased fertility of heifers. The experimental use of a C. abortus vaccine provided evidence for immunoprotection against C. abortus-induced suppression of bovine fertility. The results of these investigations suggest that bovine Chlamydophila infection should be viewed more as pervasive, low-level infection of cattle than as rare, severe disease. Such infections proceed without apparent disease or with only subtle expressions of disease, but potentially have a large impact on bovine herd health and fertility. |
The frequency of group A bovine rotavirus (gpA BRV) in calves from 1998 to 2002 was determined by the polyacrylamide gel electrophoresis technique in 2177 faecal samples, of which 1898 samples were diarrhoeic and 279 were of normal consistency (control group) that were collected from asymptomatic calves for comparative purposes. The animals were from beef and dairy cattle herds (n = 321) from 158 counties in seven States (Paraná, São Paulo, Minas Gerais, Mato Grosso do Sul, Mato Grosso, Goiás and Rondônia) and four Brazilian geographical regions (south, south-east, centre-west, and north). GpA BRV was detected in 19.4% (369/1898; p = 0.0001) of the samples collected in calves with diarrhoea and in only 2.2% (6/279; p = 0.0001) of the faeces with normal consistency. The proportion of positive samples collected from beef and dairy cattle herds was 22.8% (205/899; p = 0.0001) and 16.4% (169/999; p = 0.0005), respectively. In relation to age, a higher prevalence of infections was found in calves up to 30 days old, where 33.0% (189/573; p = 0.0001) and 20.2% (138/683; p = 0.0001) of the diarrhoeic faecal samples from beef and dairy cattle herds, respectively, were positive for gpA BRV. These results show the possible importance of inclusion of gpA BRV in the management of neonatal calf diarrhoea in Brazilian cattle herds. |
In order to show that the newly developed K-string composition distance method, based on counting oligopeptide frequencies, for inferring phylogenetic relations of prokaryotes works equally well without requiring the whole proteome data, we used all ribosomal proteins and the set of aminoacyl tRNA synthetases for each species. The latter group has been known to yield inconsistent trees if used individually. Our trees are obtained without making any sequence alignment. Altogether 16 Archaea, 105 Bacteria and 2 Eucarya are represented on the tree. Most of the lower branchings agree well with the latest, 2003, Outline of the second edition of the Bergey’s Manual of Systematic Bacteriology and the trees also suggest some relationships among higher taxa. |
A way to study the mutation pattern is to convert a 20-letter protein sequence into a scalar protein sequence, because the 20-letter protein sequence is neither vector nor scalar while a promising way to study patterns is in numerical domain. In this study, we use the amino-acid pair predictability to convert α-galactosidase A with its 137 mutations into scalar sequences, and analyse which amino-acid pairs are more sensitive to mutation. Our results show that the unpredictable amino-acid pairs are more sensitive to mutation, and the mutation trend is to narrow the difference between predicted and actual frequency of amino-acid pairs. |
The tandem of humanized variable VL and VH genes (ScFv fragment 4D5) possessing a high affinity to the HER-2/neu oncogene (the epidermal growth factor receptor expressed in many types of human tumors) was attached through a flexible linker to the second exon of human antibodies of IgG or IgE isotypes constant gene. The humanized construct of IgE isotype was generated for the first time. Genes of the recombinant antibodies were cloned into the pCl-neo vector under the control of universal cytomegalovirus (CMV) promoter. Transfected HEK-293 cells efficiently produced antibodies of the corresponding isotypes IgE and IgG1. The results of Western blotting confirmed homogeneity of the expressed antibodies, which had the predicted molecular weight and specifically interacted with the HER-2/neu. The attachment of leader peptide to the 5′-end of the gene resulted in the preferential accumulation of recombinant antibodies in the cultural medium. These results indicate that de novo constructed humanized immunoglobulin genes express functionally active, single-chain recombinant antibodies in eukaryotic cells. |
We have synthesized water-soluble complexes between the antiviral drug arbidol and polymer compounds with molecular masses of 19–31 kDa representing copolymers of acrylamide (AA) and 2-acrylamido-2-methylpropanesulfonic acid (AAMPS). The complexes are less toxic than arbidol and retain the high level of antiviral activity of this drug. The content of arbidol in the obtained complexes is within 26.4–32.1 mass%. The antiviral activity of the synthesized polymeric complexes against all studied viruses, including human epidemic influenza virus A (H3N2), bird highly pathogenic influenza virus A (H5N1), herpes type 1 virus (HSV-1), and adenovirus type III (AV-III) is comparable to the antiviral effect of nonmodified arbidol. The in vitro toxicity of the obtained complexes is about one order of magnitude lower than that of nonmodified arbidol; the pharmacological index, four times that of the initial low-molecular-weight drug. The synthesized water-soluble polymer complexes of arbidol can be useful in pharmacology since they can serve as the basis for new effective and safe parent antiviral substances and related formulations. |
Immunity to diseases is conferred by pathogen-specific memory cells that prevent disease reoccurrences. A broad repertoire of memory T-cells must be developed and maintained to effectively protect against viral invasions; yet, the total number of memory T-cells is constrained between infections. Thus, creating memory to new infections can require attrition of some existing memory cells. Furthermore, some viruses induce memory T-cell death early in an infection, after which surviving cells proliferate to refill the memory compartment. We develop mathematical models of cellular attrition and proliferation in order to examine how new viral infections impact existing immunity. With these probabilistic models, we qualitatively and quantitatively predict how the composition and diversity of the memory repertoire changes as a result of viral infections. In addition, we calculate how often immunity to prior diseases is lost due to new infections. Comparing our results across multiple general infection types allows us to draw conclusions about, which types of viral effects most drastically alter existing immunity. We find that early memory attrition does not permanently alter the repertoire composition, while infections that spark substantial new memory generation drastically shift the repertoire and hasten the decline of existing immunity. |
A logistic model was employed to correlate the outbreak of highly pathogenic avian influenza (HPAI) with related environmental factors and the migration of birds. Based on MODIS data of the normalized difference vegetation index, environmental factors were considered in generating a probability map with the aid of logistic regression. A Bayesian maximum entropy model was employed to explore the spatial and temporal correlations of HPAI incidence. The results show that proximity to water bodies and national highways was statistically relevant to the occurrence of HPAI. Migratory birds, mainly waterfowl, were important infection sources in HPAI transmission. In addition, the HPAI outbreaks had high spatiotemporal autocorrelation. This epidemic spatial range fluctuated 45 km owing to different distribution patterns of cities and water bodies. Furthermore, two outbreaks were likely to occur with a period of 22 d. The potential risk of occurrence of HPAI in Mainland China for the period from January 23 to February 17, 2004 was simulated based on these findings, providing a useful meta-model framework for the application of environmental factors in the prediction of HPAI risk. |
1. Develop strategies to quickly increase the objective knowledge about social and economic systems. 2. Describe requirements for efficient large-scale scientific data mining of anonymized social and economic data. 3. Formulate strategies how to collect stylized facts extracted from large data set. 4. Sketch ways how to successfully build up centers for computational social science. 5. Propose plans how to create centers for risk analysis and crisis forecasting. 6. Elaborate ethical standards regarding the storage, processing, evaluation, and publication of social and economic data. |
Nucleopolyhedrovirus (NPV) is divided into Group I and Group II based on the phylogenetic analysis. It has been reported that Group I NPVs such as Autographa californica multiple NPV (AcMNPV) can transduce mammalian cells, while Group II NPVs such as Helicoverpa armigera single NPV (HaSNPV) cannot. Here we report that AcMNPV was capable of stimulating antiviral activity in human hepatoma cells (SMMC-7721) manifested by inhibition of Vesicular Stomatitis virus (VSV) replication. In contrast, the HaSNPV and the Spodoptera exigua multiple NPV (SeMNPV) of group II had no inhibitory effect on VSV. Recombinant AcMNPV was shown to induce interferons alpha/beta even in the absence of transgene expression in human SMMC-7721 cells, while it mediated transgene expression in BHK and L929 mammalian cells without an ensuing antiviral activity. |
Sustainability science is emerging as a transdisciplinary effort to come to grips with the much-needed symbiosis between human activity and the environment. While there is recognition that conventional economic growth must yield to policies that foster sustainable development, this has not yet occurred on any broad scale. Rather, there is clear evidence that the Earth’s ecosystems and landscapes continue to degrade as a consequence of the cumulative impact of human activities. Taking an ecohealth approach to sustainability science provides a unique perspective on both the goals and the means to achieve sustainability. The goals should be the restoration of full functionality to the Earth’s ecosystems and landscapes, as measured by the key indicators of health: resilience, organization, vitality (productivity), and the absence of ecosystem distress syndrome. The means should be the coordinated (spatially and temporally) efforts to modify human behaviors to reduce cumulative stress impacts. Achieving ecosystem health should become the cornerstone of sustainability policy—for healthy ecosystems are the essential precondition for achieving sustainable livelihoods, human health, and many other societal objectives, as reflected in the Millennium Development Goals. |
This article makes a contribution to the on-going debates about universalism and cultural relativism from the perspective of sociology. We argue that bioethics has a universal range because it relates to three shared human characteristics,—human vulnerability, institutional precariousness and scarcity of resources. These three components of our argument provide support for a related notion of ‘weak foundationalism’ that emphasizes the universality and interrelatedness of human experience, rather than their cultural differences. After presenting a theoretical position on vulnerability and human rights, we draw on recent criticism of this approach in order to paint a more nuanced picture. We conclude that the dichotomy between universalism and cultural relativism has some conceptual merit, but it also has obvious limitations when we consider the political economy of health and its impact on social inequality. |
Demands for effective vaccines to control parasitic diseases of humans and livestock have been recently exacerbated by the development of resistance of most pathogenic parasites to anti-parasitic drugs. Novel genomic and proteomic technologies have provided opportunities for the discovery and improvement of DNA vaccines which are relatively easy as well as cheap to fabricate and stable at room temperatures. However, their main limitation is rather poor immunogenicity, which makes it necessary to couple the antigens with adjuvant molecules. This paper review recent advances in the development of DNA vaccines to some pathogenic protozoa and helminths. Numerous studies were conducted over the past 14 years of 21(st) century, employing various administration techniques, adjuvants and new immunogenic antigens to increase efficacy of DNA vaccines. Unfortunately, the results have not been rewarding. Further research is necessary using more extensive combinations of antigens; alternate delivery systems and more efficient adjuvants based on knowledge of the immunomodulatory capacities of parasitic protozoa and helminths. |
Scientific research is subject to a number of regulations which impose incidental (time, place), rather than substantive (type of research), restrictions on scientific research and the knowledge created through such research. In recent years, however, the premise that scientific research and knowledge should be free from substantive regulation has increasingly been called into question. Some have suggested that the law should be used as a tool to substantively restrict research which is dual-use in nature or which raises moral objections. There are, however, some problems with using law to restrict or prohibit certain types of scientific research, including (i) the inherent imprecision of law for regulating complex and rapidly evolving scientific research; (ii) the difficulties of enforcing legal restrictions on an activity that is international in scope; (iii) the limited predictability of the consequences of restricting specific branches of scientific research; (iv) inertia in the legislative process; and (v) the susceptibility of legislators and regulators to inappropriate factors and influence. Rather than using law to restrict scientific research, it may be more appropriate and effective to use a combination of non-traditional legal tools including norms, codes of conduct, restrictions on publication, and scientist-developed voluntary standards to regulate problematic scientific research. |
Motivated by the need to include the different characteristics of individuals and the damping effect in predictions of epidemic spreading, we build a model with variant coefficients and white Gaussian noise based on the traditional SIR model. The analytic and simulation results predicted by the model are presented and discussed. The simulations show that using the variant coefficients results in a higher percentage of susceptible individuals and a lower percentage of removed individuals. When the noise is included in the model, the percentage of infected individuals has a wider peak and more fluctuations than that predicted using the traditional SIR model. |
In this paper, we present a fuzzy approach to the Reed–Frost model for epidemic spreading taking into account uncertainties in the diagnostic of the infection. The heterogeneities in the infected group is based on the clinical signals of the individuals (symptoms, laboratorial exams, medical findings, etc.), which are incorporated into the dynamic of the epidemic. The infectivity level is time-varying and the classification of the individuals is performed through fuzzy relations. Simulations considering a real problem with data of the viral epidemic in a children daycare are performed and the results are compared with a stochastic Reed–Frost generalization. |
Gold-coated iron oxide nanoparticle Hepatitis B virus (HBV) DNA probes were prepared, and their application for HBV DNA measurement was studied. Gold-coated iron oxide nanoparticles were prepared by the citrate reduction of tetra-chloroauric acid in the presence of iron oxide nanoparticles which were added as seeds. With a fluorescence-based method, the maximal surface coverage of hexaethiol 30-mer oligonucleotides and the maximal percentage of hybridization strands on gold-coated iron oxide nanoparticles were (120 ± 8) oligonucleotides per nanoparticle, and (14 ± 2%), respectively, which were comparable with those of (132 ± 10) and (22 ± 3%) in Au nanoparticle groups. Large network aggregates were formed when gold-coated iron oxide nanoparticle HBV DNA gene probe was applied to detect HBV DNA molecules as evidenced by transmission electron microscopy and the high specificity was verified by blot hybridization. Our results further suggested that detecting DNA with iron oxide nanoparticles and magnetic separator was feasible and might be an alternative effective method. |
When our knowledge of a field accumulates to a certain level, we are bound to see the rise of one or more great scientists. They will make a series of grand discoveries/breakthroughs and push the discipline into an ‘age of grand discoveries’. Mathematics, geography, physics and chemistry have all experienced their ages of grand discoveries; and in life sciences, the age of grand discoveries has appeared countless times since the 16th century. Thanks to the ever-changing development of molecular biology over the past 50 years, contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be ‘lifeomics’. At the end of the 20th century, genomics wrote out the ‘script of life’; proteomics decoded the script; and RNAomics, glycomics and metabolomics came into bloom. These ‘omics’, with their unique epistemology and methodology, quickly became the thrust of life sciences, pushing the discipline to new high. Lifeomics, which encompasses all omics, has taken shape and is now signalling the dawn of a new era, the age of grand discoveries. |
The evolving Ebola epidemic in West Africa is unprecedented in its size and scope, requiring the rapid mobilization of resources. It is too early to determine all of the ethical challenges associated with the outbreak, but these should be monitored closely. Two issues that can be discussed are (1) the decision to implement and evaluate unregistered agents to determine therapeutic or prophylactic safety and efficacy and (2) the justification behind this decision. In this paper, I argue that it is not compassionate use that justifies this decision and suggest three lines of reasoning to support the decision. |
Vaccines are the mainstay of influenza prevention. In the treatment of a likely or certain case of influenza, ion channel inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) can be effective in reducing the duration of illness in adults. In the absence of a likely or certain influenza diagnosis, ion channel inhibitors or neuramindase inhibitors have lower effectiveness, and symptom relief becomes the rationale for treatment of influenza-like illness. Because both influenza and influenzalike illness are self-limiting, safety of interventions is paramount, especially in children. Echinacea extracts, steam, chicken soup, ipatropium bromide, and oxymetazoline in adults are the interventions that appear to have the best empirical evidence. |
BACKGROUND, AIMS AND SCOPE: Current studies have paid little attention to the dynamism in urban spatial expansion and its possible environmental and health effects or to the health effects of rapid urban environmental change at different points along the urbanisation gradient. This study adopts a public health ecology approach to systematically understand the relationship between urbanisation, urban environmental change and human health in China. METHOD: Remote sensing image analysis, based on night light data at five different time periods in recent decades, was used to determine changes to the overall urban area. Through a review of the evidence on the relationships between environmental health, urbanisation and health, we advance a pathway framework for explaining urban human health ecology. The Spearman rank correlation coefficient was used to measure the correlation between disease prevalence and urbanisation level, adding a further dimension to a systemic understanding of urban health. RESULTS AND CONCLUSIONS: Urban areas have been increasing spatially, but unevenly, in recent decades, with medium and small cities also expanding rapidly in the past decade. Urbanisation and urban expansion result in changes to land use/coverage change, the urban environment and the residents’ lifestyle, which result in human health problems. Regions with the highest urbanisation level were more inclined to have a high prevalence of chronic disease in recent decades. An ecological public health approach provides insights into the multiple types of data which need to be routinely collected if human disease is not to become a barrier to social and economic development. |
RNA interference (RNAi) causes degradation of targeted endogenous RNA in many diverse organisms. To investigate the effect of dsRNA on silkworm cells, we transfected three kinds of synthetic dsRNAs of 435 bp(Ap(1)), 300 bp(Ap(2)) and 399 bp(A(H)) in length against the various regions of BmNPV’s DNA polymerase gene and DNA helicase gene, which are indispensable for viral replication in silkworm cells by TransMessenger(TM) transfection Reagent. Results indicated that in the experiment where silkworm cells were infected with wild-strain BmNPV of the three dsRNAs, Ap(2) and A(H) can effectively suppress the replication of virus, but Ap(1) had no effect on the inhibition of viral replication. Ap(2) and A(H) can reduce the infective titer of BmNPV with a peak change of approximately 3–4 logs on day 4 post-infection. The results of reverse transcript polymerase chain reaction (RT-PCR) and DNA dot blotting also indicated that the expression level of the two target genes and the quantity of viral DNA both distinctly decreased under the influence of Ap(2) or A(H). Furthermore, using fluorescence microscopy we analyzed the distribution patterns of dsRNA. Our studies revealed that a majority of dsRNA was localized in the nuclear periphery discontinuously after 24 h of transfection. |
Two small random peptide libraries, one composed of 4550 dodecapeptides and one of 8000 tripeptides, were synthesized in newly developed credit-card format miniPEPSCAN cards (miniPEPSCAN libraries). Each peptide was synthesized in a discrete well (455 peptides/card). The two miniPEPSCAN libraries were screened with three different monoclonal antibodies (Mabs). Two other random peptide libraries, expressed on the wall of bacteria (recombinant libraries) and composed of 10(7) hexa- and octapeptides, were screened with the same three Mabs. The aim of this study was to compare the amino acid sequence of peptides selected from small and large pools of random peptides and, in this way, investigate the potential of small random peptide libraries. The screening of the two miniPEPSCAN libraries resulted in the identification of a surprisingly large number of antibody-binding peptides, while the screening of the large recombinant libraries, using the same Mabs, resulted in the identification of only a small number of peptides. The large number of peptides derived from the small random peptide libraries allowed the determination of consensus sequences. These consensus sequences could be related to small linear and nonlinear parts of the respective epitopes. The small number of peptides derived from the large random peptide libraries could only be related to linear epitopes that were previously mapped using small libraries of overlapping peptides covering the antigenic protein. Thus, with respect to the cost and speed of identifying peptides that resemble linear and nonlinear parts of epitopes, small diversity libraries based on synthetic peptides appear to be superior to large diversity libraries based on expression systems. |
A stochastic SIRS epidemic model with nonlinear incidence rate and varying population size is formulated to investigate the effect of stochastic environmental variability on inter-pandemic transmission dynamics of influenza A. Sufficient conditions for extinction and persistence of the disease are established. In the case of persistence, the existence of endemic stationary distribution is proved and the distance between stochastic solutions and the endemic equilibrium of the corresponding deterministic system in the time mean sense is estimated. Based on realistic parameters of influenza A in humans, numerical simulations have been performed to verify/extend our analytical results. It is found that: (i) the deterministic threshold of the influenza A extinction [Formula: see text] may exist and the threshold parameter will be overestimated in case of neglecting the impaction of environmental noises; (ii) the presence of environmental noises is capable of supporting the irregular recurrence of influenza epidemic, and the average level of the number of infected individuals I(t) always decreases with the increase in noise intensity; and (iii) if [Formula: see text] , the volatility of I(t) increases with the increase of noise intensity, while the volatility of I(t) decreases with the increase in noise intensity if [Formula: see text] . |
Methods have been developed for culturing a dividing population of morphologically differentiated rat parotid, lacrimal, and pancreatic acinar cells in vitro. Isolated acinar cells were plated onto tissue culture dishes coated with a three-dimensional, reconstituted basement membrane gel. After attachment in Ham’s nutrient mixture F12, the cells were cultured at 35°C in F12 supplemented with 10% heat inactivated rat serum, epidermal growth factor, dexamethasone, insulin, transferrin, selenium, putrescine, reduced glutathione, ascorbate, penicillin, streptomycin, and the appropriate secretagogue. Under these conditions, the cells attached rapidly and DNA synthesis was initiated within 2 to 3 d. Although the cells flattened on the substratum, they continued to maintain their differentiated morphology. The cells contained secretory granules, and the secretory enzymes peroxidase and amylase could be detected. The use of a reconstituted basement membrane gel proved critical for the attachment and growth of exocrine acinar cells. |
The use of antiviral drugs has been recognized as the primary public health strategy for mitigating the severity of a new influenza pandemic strain. However, the success of this strategy requires the prompt onset of therapy within 48 hours of the appearance of clinical symptoms. This requirement may be captured by a compartmental model that monitors the density of infected individuals in terms of the time elapsed since the onset of symptoms. We show that such a model can be expressed by a system of delay differential equations with both discrete and distributed delays. The model is analyzed to derive the criterion for disease control based on two critical factors: (i) the profile of treatment rate; and (ii) the level of treatment as a function of time lag in commencing therapy. Numerical results are also obtained to illustrate the feasible region of disease control. Our findings show that due to uncertainty in the attack rate of a pandemic strain, initiating therapy immediately upon diagnosis can significantly increase the likelihood of disease control and substantially reduce the required community-level of treatment. This suggests that reliable diagnostic methods for influenza cases should be rapidly implemented within an antiviral treatment strategy. |
Statutes criminalizing behavior that risks transmission of HIV/AIDS exemplify use of the criminal law against individuals who are victims of infectious disease. These statutes, despite their frequency, are misguided in terms of the goals of the criminal law and the public health aim of reducing overall burdens of disease, for at least three important reasons. First, they identify individual offenders for punishment, a paradigm that is misplaced in the most typical contexts of transmission of infectious disease and even for HIV/AIDS, despite claims of AIDS exceptionalism. Second, although there are examples of individuals who transmit infectious disease in a manner that fits the criminal law paradigm of identification of individual offenders for deterrence or retribution, these examples are limited and can be accommodated by existing criminal laws not devoted specifically to infectious disease. Third, and most importantly, the current criminal laws regarding HIV/AIDS, like many other criminal laws applied to infectious disease transmission, have been misguided in focusing on punishment of the diseased individual as a wrongful transmitter. Instead of individual offenders, activities that enhance the scale of disease transmission—behaviors that might be characterized as ‘transmission facilitation’—are a more appropriate target for the criminal law. Examples are trafficking in human beings (including sex trafficking, organ trafficking, and labor trafficking), suppression of information about the emergence of infection in circumstances in which there is a legally established obligation to disclose, and intentional or reckless activities to discourage disease treatment or prevention. Difficulties remain with justifications for criminalizing even these behaviors, however, most importantly the need for trust in reducing overall burdens of disease, problems in identifying individual responsible offenders, and potential misalignment between static criminal law and the changing nature of infectious disease. |
We study the final size equation for an epidemic in a subdivided population with general mixing patterns among subgroups. The equation is determined by a matrix with the same spectrum as the next generation matrix and it exhibits a threshold controlled by the common dominant eigenvalue, the basic reproduction number [Formula: see text]: There is a unique positive solution giving the size of the epidemic if and only if [Formula: see text] exceeds unity. When mixing heterogeneities arise only from variation in contact rates and proportionate mixing, the final size of the epidemic in a heterogeneously mixing population is always smaller than that in a homogeneously mixing population with the same basic reproduction number [Formula: see text]. For other mixing patterns, the relation may be reversed. |
Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein. Imatinib is the first-line treatment of CML; however, many patients are resistant to this drug. In this study, we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments. GSE24946 was downloaded from the GEO database, which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5). Three drug treatment groups were considered for this study: arsenic trioxide (ATO), AMN107, and ATO+AMN107. Each group had one sample at each time point (3, 12, 24, and 48 h). Time-series genes with a ratio of standard deviation/average (coefficient of variation) >0.15 were screened, and their expression patterns were revealed based on Short Time-series Expression Miner (STEM). Then, the functional enrichment analysis of time-series genes in each group was performed using DAVID, and the genes enriched in the top ten functional categories were extracted to detect their expression patterns. Different time-series genes were identified in the three groups, and most of them were enriched in the ribosome and oxidative phosphorylation pathways. Time-series genes in the three treatment groups had different expression patterns and functions. Time-series genes in the ATO group (e.g. CCNA2 and DAB2) were significantly associated with cell adhesion, those in the AMN107 group were related to cellular carbohydrate metabolic process, while those in the ATO+AMN107 group (e.g. AP2M1) were significantly related to cell proliferation and antigen processing. In imatinib-resistant CML cells, ATO could influence genes related to cell adhesion, AMN107 might affect genes involved in cellular carbohydrate metabolism, and the combination therapy might regulate genes involved in cell proliferation. |
Although the currently available vaccines represent an outstanding success story in modern medicine and have had a dramatic effect on morbidity and mortality worldwide, it is clear that improvements are required in the current vaccine delivery technologies. Improvements are required to enable the successful development of vaccines against infectious diseases that have so far proven difficult to control with conventional approaches. Improvements may include the addition of novel injectable adjuvants or the use of novel routes of delivery, including mucosal immunization. Mucosal delivery may be required to provide protection against pathogens that infect at mucosal sites, including sexually transmitted diseases. Alternatively, novel approaches to delivery, including mucosal administration, may be used to improve compliance for existing vaccines. Of particular interest for safer mass immunization campaigns are needle-free delivery devices, which would avoid problems due to needle re-use in many parts of the world and would avoid needle-stick injuries. |
The objective of this study was to establish a method by which trophectodermal cells originating from individual preimplantation bovine embryos could be perpetuated in monolayer culture. A single, Day-11 bovine embryo collected nonsurgically from a mixed-breed beef cow was cultured in Ham's F10 medium supplemented with fetal bovine serum, sodium pyruvate, insulin and epidermal growth factor. After 13 d in culture the embryo had adhered to the surface of the plastic culture vessel and a monolayer covering 0.3 cm(2) had developed in the manner of a tissue explant. The monolayer was successfully dispersed using trypsin-EDTA and the cells were passaged Expansion to a 25-cm(2) flask was achieved by the 4th passage. By passaging cultures at a dilution ratio of 1∶2, cells were maintained for 38 passages before growth slowed. Transfers beyond the 44th passage were unsuccessful. The cell line, designated BE-13, was successfully frozen and thawed at the 9th, 12th, 15th, and 20th passages. The cell line contains both mono- and binucleate cells with a prominent rough endoplasmic reticulum characteristic of ruminant trophoblast cells. Susceptibility to eight bovine viruses was demonstrated. Such cell lines may provide inexpensive systems for the study of trophoblast metabolism and for investigation of the role of the trophoblast in the pathogenesis of selected bovine abortifacient diseases. Because of their range of viral susceptibility, these cells might also be useful for diagnostic purposes. |
Cystoisospora suis is a pathogen that causes diarrhea in pigs and can lead to serious disease. Species identification, especially by histopathological examination, is often difficult because of morphologically similar parasites such as Eimeria species. In this study, we used histopathological, bacteriological, virological, and parasitological methods to identify the cause of the disease in two piglets with severe diarrhea. Villous atrophy, diffuse necrosis, and flattening of mucosal epithelial cells were found in the ilea of examined piglets, and coccidian parasites were found in the cytoplasm of the epithelial cells. In some merozoites in the meronts, the presence of two nuclei indicated type 1 merozoites, characteristic of C. suis. According to Cystoisospora-specific PCR targeting the rRNA internal transcribed spacer 1 (ITS1) gene, the sequences of the products were 98.5% similar to those of C. suis. Escherichia coli (O149 serogroup) exhibiting a virulence factor profile (LT, STb, and EAST1 as toxins and F4 as a colonization factor) was detected in one piglet. No other bacteria or significant enteric viruses were found. Co-infection with C. suis and E. coli could imply aggravation of the disease, although further study is needed to assess the pathogenicity of this interaction. This study is the first to clarify by molecular analysis the sequences of C. suis detected in piglets in Japan. |
An informational landscape refers to an array of information related to a particular theme or function. The Internet is an example of an informational landscape designed by humans for purposes of communication. Once it exists, however, any informational landscape may be exploited to serve a new purpose. Listening Post is the name of a dynamic multimedia work of art that exploits the informational landscape of the Internet to produce a visual and auditory environment. Here, I use Listening Post as a prototypic example for considering the creative role of informational landscapes in the processes that beget evolution and science. |
Explant cultures of bovine mammary tissue taken from virgin heifers were used to examine adherence, colonization and cytopathogenesis ofStreptococcus uberis, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus andEscherichia coli in the putative target tissue. None of the five bacteria was able to adhere to healthy ductular epithelium but all showed a marked tropism for exposed connective tissue.S. aureus andE. coli induced a marked cytopathic effect in ductular epithelium after 6 hours in culture but the bacteria were not in close association with the affected tissue. No evidence could be found to support the hypothesis that adherence to epithelium might be the first stage in the pathogenesis of mastitis caused by these organisms. |
A multi-patch SEIQR epidemic model is formulated to investigate the long-term impact of entry–exit screening measures on the spread and control of infectious diseases. A threshold dynamics determined by the basic reproduction number [Formula: see text] is established: The disease can be eradicated if [Formula: see text] , while the disease persists if [Formula: see text] . As an application, six different screening strategies are explored to examine the impacts of screening on the control of the 2009 influenza A (H1N1) pandemic. We find that it is crucial to screen travelers from and to high-risk patches, and it is not necessary to implement screening in all connected patches, and both the dispersal rates and the successful detection rate of screening play an important role on determining an effective and practical screening strategy. |
Infection age is often an important factor in epidemic dynamics. In order to realistically analyze the spreading mechanism and dynamical behavior of epidemic diseases, in this paper, a generalized disease transmission model of SIS type with age-dependent infection and birth and death on a heterogeneous network is discussed. The model allows the infection and recovery rates to vary and depend on the age of infection, the time since an individual becomes infected. We address uniform persistence and find that the model has the sharp threshold property, that is, for the basic reproduction number less than one, the disease-free equilibrium is globally asymptotically stable, while for the basic reproduction number is above one, a Lyapunov functional is used to show that the endemic equilibrium is globally stable. Finally, some numerical simulations are carried out to illustrate and complement the main results. The disease dynamics rely not only on the network structure, but also on an age-dependent factor (for some key functions concerned in the model). |
The authors’ studies on the organization and variation of plant genome with the use of molecular markers are briefly reviewed with special emphasis on random amplified polymorphic DNA (RAPD), inter simple sequence repeat (ISSR), sequence characterized amplified region (SCAR), and cleaved amplified polymorphic sequence (CAPS) markers detected with the use of polymerase chain reaction (PCR). These markers have been demonstrated to be promising for identifying cultivars and determining the purity of genetic strains of pea. Genetic relationships between strains, cultivars, and mutants of pea have been studied. The role of molecular markers in molecular genetic mapping and localizing the genes of commercially important characters of pea has been shown. The possibility of the use of molecular markers for studying somaclonal variation and detecting mutagenic factors in plants during long-term spaceflights is considered. The prospects of using DNA markers for understanding the organization and variability of higher plant genomes are discussed. |
Anthropogenic stress on the earth’s ecosystems has resulted in widespread prevalence of ecosystem distress syndrome, a quantifiable set of signs of ecosystem degradation. At the same time, the planet is witnessing rapid declines in global cultural diversity and in the vitality of the world’s cultures, which closely mirror, and are interrelated with, ecological degradation. As a consequence of this converging crisis of loss of ecosystem and cultural health, global health and sustainability are increasingly under threat. An eco-cultural health perspective based on understanding the linkages between human activities, ecological and cultural disruption, and public health is essential for addressing these threats and achieving global sustainability. |
In this study, the relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents, and dinucleotide were used to investigate codon usage pattern of each protein-coding gene and genome among 31 Newcastle disease virus (NDV) isolates. The result shows that the overall extent of codon usage bias in NDV is low (mean ENC = 56.15 > 40). The good correlation between the (C + G)(12)% and (G + C)(3)% suggests that the mutational pressure, rather than natural selection, is the main factor that determines the codon usage bias and base component in NDV. It is observed that synonymous codon usage pattern in NDV genes is gene function and geography specific, but not host specific. By contrasting synonymous codon usage patterns of different NDV isolates, we suggest that more than one genotype of NDV circulates in waterfowl in USA; and gene length has no significant effect on the variations of synonymous codon usage in these virus genes. CpG under-represented is a characteristic for NDV to fit in its host. These results not only provide an insight into the variation of codon usage pattern among the genomes of NDV, but also may help in understanding the processes governing the evolution of NDV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-011-0574-z) contains supplementary material, which is available to authorized users. |
This paper primarily argues that Epidemiology is Ecosystem Science. It will not only explore this notion in detail but will also relate it to the argument that Classical Chinese Medicine was/is Ecosystem Science. Ecosystem Science (as instantiated by Epidemiology) and Ecosystem Science (as instantiated by Classical Chinese Medicine) share these characteristics: (a) they do not subscribe to the monogenic conception of disease; (b) they involve multi variables; (c) the model of causality presupposed is multi-factorial as well as non-linear. |
This study aimed to analyze main groups accused on social media of causing or spreading the 2014–2016 Ebola epidemic in West Africa. In this analysis, blame is construed as a vehicle of meaning through which the lay public makes sense of an epidemic, and through which certain classes of people become “figures of blame”. Data was collected from Twitter and Facebook using key word extraction, then categorized thematically. Our findings indicate an overall proximate blame tendency: blame was typically cast on “near-by” figures, namely national governments, and less so on “distant” figures, such as generalized figures of otherness (“Africans”, global health authorities, global elites). Our results also suggest an evolution of online blame. In the early stage of the epidemic, blame directed at the affected populations was more prominent. However, during the peak of the outbreak, the increasingly perceived threat of inter-continental spread was accompanied by a progressively proximal blame tendency, directed at figures with whom the social media users had pre-existing biopolitical frustrations. Our study proposes that pro-active and on-going analysis of blame circulating in social media can usefully help to guide communications strategies, making them more responsive to public perceptions. |
This paper examines the impact of trade openness and foreign direct investment (FDI) on life expectancy using time series data over the period of 1972–2013. We have applied structural break unit root as well as cointegration tests to examine integrating properties of the variables and cointegration among the variables. The causal linkage between the variables has been tested by applying the VECM Granger causality. The empirical evidence confirms the presence of cointegration amid the variables. Moreover, trade openness and FDI increase population health measured by life expectancy in the long-run. Furthermore, the analysis suggests that trade openness and FDI cause life expectancy in the short-run. These findings have several policy implications to improve life expectancy for the people of Pakistan in particular and other developing countries in general. |
Transgenic tobacco plants (ppa-1) constitutively expressing Escherichia coli pyrophosphatase behind the 35S CaMV promoter accumulate high levels of soluble sugars in their leaves [27]. These plants were considered a tool to study adaptation of leaves to photoassimilate accumulation at the molecular level. By differential hybridization of a subtractive library enriched for transcripts present in the transgenic plants 12 different cDNAs were isolated. By sequence analysis four cDNAs could be identified as 1-aminocyclopropane-1-carboxylate-oxidase and as three different pathogenesis-related proteins (PR-1b, PR-Q and SAR 8.2). Two cDNAs were homologous to a calmodulin-like protein from Arabidopsis and a human ribosomal protein L19 while six cDNA clones remained unknown. One of these clones (termed PAR-1 for photoassimilate-responsive) displayed features similar to pathogenesis-related proteins: Hybridizing transcripts, 1.2 and 1.0 kb in length, were strongly inducible by salicylate and accumulated in tobacco plants after infection with potato virus Y (PVY) both in infected and uninfected systemic leaves. PAR-1 transcripts also accumulated in wildtype leaves upon floating on glucose and sucrose whereas sorbitol and polyethylene glycol had no effect. Rescreening of the ppa-1 cDNA library with the PAR-1 cDNA as probe resulted in 25 hybridizing cDNAs which by homology were found to fall into three classes (PAR-1a, b, c). The cDNAs coding for PAR-1a and b were 90.6% homologous on the DNA level while both were less related to the PAR-1c cDNA (70.5% and 75.2% homologous, respectively). One open reading frame was identified in all three PAR-1 cDNA classes. Translation would result in proteins with a theoretical molecular mass of about 20 kDa. The N-terminal amino acid sequences resemble a signal peptide which would direct the proteins to the secretory pathway. Using selective 3′ hybridization probes of the three PAR-1 cDNAs it was possible to discriminate the different transcripts. Both PAR-1a and PAR-1c mRNAs are induced in plants treated with PVY. |
The accumulation of [(3)H]noradrenaline ([(3)H]NA) and its oxidation products was studied in primary cultures of cerebral astrocytes. Astroglial accumulation of radiolabeled catecholamine ([(3)H] NA and oxidation products) was enhanced by manganese or iron, but it was inhibited by unlabeled NA, dopamine or ascorbate. Tissue:medium ratios of radioactivity increased as extracellular [(3)H]NA was oxidized. When extracellular oxidation was prevented by ascorbate, as confirmed by high performance liquid chromatography with electrochemical detection, either ouabain pretreatment or nominally Na(+)-free incubation medium inhibited approximately one-half of specific [(3)H]NA accumulation by rat (but not mouse) astrocytes. These observations suggest that neurological responses to trace metals and ascorbate may arise from the effects of these agents on the clearance of extracellular catecholamines. Astrocytes can accumulate oxidation products of NA more rapidly than they take up NA itself, but ascorbate at physiological concentrations prevents the oxidation process in extracellular fluid. Furthermore, in the presence of ascorbate, Na(+)-dependent transport mediates a significant component of NA accumulation in rat astrocytes. |
The nucleocapsid (N) gene of the porcine epidemic diarrhea virus (PEDV) Chinju99 which was previously isolated in Chinju, Korea was cloned and sequenced to establish the information for the development of genetically engineered diagnostic reagents. Also, sequences of the nucleotides and deduced amino acids of the Chinju99 N gene were analyzed by alignment with those of CV777 and Br1/87. The nucleotide sequence encoding the entire N gene open reading frame (ORF) of Chinju99 was 1326 bases long and encoded a protein of 441 amino acids with predicted M (r) of 49 kDa. It consisted of 405 adenine (30.5%), 293 cytosine (22.1%), 334 guanines (25.2%) and 294 thymines (22.2%) residues. The Chinju99 N ORF nucleotide sequence was 96.5% and 96.4% homologous with that of the CV777 and Br1/87, respectively. The Chinju99 N protein revealed 96.8% amino acid identity with that of Br1/87 and CV777, respectively. The amino acid sequence contained seven potential sites for threonine (T)- or serine (S)-linked phosphorylation by each protein kinase C and casein kinase II. |
An overview of the principles of the polymerase chain reaction, ligase chain reaction, self-sustained sequence replication and Qβ replicase is given. The application of these methods for the diagnosis of veterinary infectious and hereditary diseases as well as for other diagnostic purposes is discussed and comprehensive tables of reported assays are provided. Specific areas where these DNA-based amplification methods provide substantial advantages over traditional approaches are also highlighted. With regard to PCR-based assays for the detection of viral pathogens, this article is an update of a previous review by Belák and Ballagi-Pordány (1993). |
The role of an A/T-rich positive regulatory region (P268, -444 to -177 from the translation start site) of the pea plastocyanin gene (PetE) promoter has been investigated in transgenic plants containing chimeric promoters fused to the β-glucuronidase (GUS) reporter gene. This region enhanced GUS expression in leaves of transgenic tobacco plants when fused in either orientation to a minimal pea PetE promoter (-176 to +4) and in roots when fused in either orientation upstream or downstream of a minimal cauliflower mosaic virus 35S promoter (-90 to +5). The region was also able to enhance GUS expression in microtubers of transgenic potato plants when placed in either orientation upstream of a minimal class I patatin promoter (-332 to +14). Dissection of P268 revealed that cis elements responsible for enhancing GUS expression from the minimal PetE promoter were distributed throughout P268. Multiple copies of a 31 bp A/T-rich sequence from within P268 and of a 26 bp random A/T sequence were able to enhance GUS expression from the minimal PetE promoter, indicating that A/T-rich sequences are able to act as quantitative, non-tissue-specific enhancer elements in higher plants. Abbreviations: CaMV, cauliflower mosaic virus; GUS, β-glucuronidase; HMG, high-mobility group; MAR, matrix-associated region; MU, methylumbelliferone; SAR, scaffold-associated region. |
Ammonia has been considered the contaminant primarily responsible for respiratory disease in poultry. Even though it can cause tracheal lesions, its adverse effects on the trachea have not been sufficiently studied. The present study investigated tracheal changes in Arbor Acres broilers (Gallus gallus) induced by high concentration of ammonia using isobaric tag for relative and absolute quantification (iTRAQ)-based proteome analysis. In total, 3,706 proteins within false discovery rate of 1% were identified, including 119 significantly differentially expressed proteins. Functional analysis revealed that proteins related to immune response and muscle contraction were significantly enriched. With respect to the immune response, up-regulated proteins (like FGA) were pro-inflammatory, while down-regulated proteins participated in antigen processing and antigen presenting (like MYO1G), immunoglobulin and cathelicidin production (like fowlicidin-2), and immunodeficiency (like PTPRC). Regarding muscle contraction, all differentially expressed proteins (like TPM1) were up-regulated. An over-expression of mucin, which is a common feature of airway disease, was also observed. Additionally, the transcriptional alterations of 6 selected proteins were analyzed by quantitative RT-PCR. Overall, proteomic changes suggested the onset of airway obstruction and diminished host defense in trachea after ammonia exposure. These results may serve as a valuable reference for future interventions against ammonia toxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-016-0202-8 and is accessible for authorized users. |
Nanotechnology is a highly promising field, with nanoparticles produced and utilized in a wide range of commercial products. Silver nanoparticles (AgNPs) has been widely used in clothing, electronics, bio-sensing, the food industry, paints, sunscreens, cosmetics and medical devices, all of which increase human exposure and thus the potential risk related to their short- and long-term toxicity. Many studies indicate that AgNPs are toxic to human health. Interestingly, the majority of these studies focus on the interaction of the nano-silver particle with single cells, indicating that AgNPs have the potential to induce the genes associated with cell cycle progression, DNA damage and mitochondrial associated apoptosis. AgNPs administered through any method were subsequently detected in blood and were found to cause deposition in several organs. There are very few studies in rats and mice involving the in vivo bio-distribution and toxicity, organ accumulation and degradation, and the possible adverse effects and toxicity in vivo are only slowly being recognized. In the present review, we summarize the current data associated with the increased medical usage of nano-silver and its related nano-materials, compare the mechanism of antibiosis and discuss the proper application of nano-silver particles. |
To measure the levels of access to continuing professional education (CPE) among the health workers, an index (continuing professional education access index: CEAI) was constructed. The CEAI is composed of six indicators: (i) availability of CPE; (ii) distribution of CPE; (iii) informational access; (iv) geographical access; (v) economic access; and (vi) preparedness to release staff. When developing the equation of the CEAI, these six component indicators were weighted in accordance with the order of importance reported by the earlier studies. To test its validity, the CEAI was applied to the CPE status in three regions of Ghana. The results of this application revealed that there was greater discrepancies in the CEAI values according to the type of health facilities. The type of health facilities with the greatest CEAI (= 0.609) implying the best access to CPE was clinics while training/research institutes resulted in the lowest CEAI (= 0.447). Regional variation among the three regions was not significant. A simple linear regression between CEAI and adjusted number of CPE opportunities per health worker produced an extremely high conformity in the model (R (2) = 0.960). This may indicate the validity of the proposed CEAI model to the large extent. |
Remaining important tasks in finding and developing new drugs and vaccines for HIV/AIDS, malaria, cancer and other diseases require continued industry research and development. Industry’s research and development pipeline has produced drugs that have saved AIDS victims previously facing certain death, but still no cure nor vaccine is yet available. Experience with the process of research and development indicates that it requires more than a decade of development to produce a new drug with costs in the hundreds of millions of dollars. Intellectual property protection is critically important in assuring that drug development continues. Partnerships between industry and the public sector have increased access to new therapies in developing countries and promise to enhance access to both patented and generic medicines in the future. |
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6C(intermediate) macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster. Protein-protein interaction network was constructed and analysed to discover the key genes. A total of 6738 DEGs were identified and assigned to 20 model profiles. DEGs in profile 13 were one of the predominant expression profiles, which are involved in immune cell chemotaxis and proliferation. Signet analysis showed that Atp5al, Atp5o, Cox4i, Cdc42, Rac2 and Nhp2 were the key genes involved in oxidation-reduction, apoptosis, migration, M1-M2 differentiation, and proliferation of macrophages. RPS18 may be an appreciate reference gene as it was stable in macrophages. The identified DEGs and their enriched pathways investigate factors that may participate in the functional changes of CD 1lb(+)Ly6C(intermediate) macrophages after renal IRI. Moreover, the vital gene Nhp2 may involve the polarization of macrophages, which may be a new target to affect the process of AKI |
The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of Orthomyxoviridae family. It encodes at least 10 proteins from eight negative-strand RNA segments. Since ISAV belongs to the same virus family as Influenza A virus, with similarities in protein functions, they may hence be characterised by analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in interferon antagonism and RNA-binding functions. In this study, we investigated the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium transient suppression assay in stably silenced transgenic Nicotiana xanthi. In addition, s8ORF2 was identified as a novel interactor with SsMov10, a key molecule responsible for RISC assembly and maturation in the RNAi pathway. This study thus sheds light on a novel route undertaken by viral proteins in promoting viral growth, using the host RNAi machinery. |
An enzyme-linked immunosorbent assay (ELISA) was developed in order to serve in detecting and speciating mycoplasmas isolated from cell cultures. Its main features included a biotin-streptavidin amplification step and a solid phase consisting of a microporous membrane. Cell samples in the form of suspensions were applied to nitrocellulose or ion exchange membranes immobilized in commerciallyavailable microtiter, multiwell manifolds. The blocking buffer contained 1% purified α-casein. The primary antibodies were monoclonal and the polyclonal secondary antibody was biotinylated. The enzyme utilized was streptavidin-horseradish peroxidase. The substrate-dye complex consisted of either 4-chloro-1-naphthol and hydrogen peroxide or ortho phenylene diamine (OPD) and hydrogen peroxide. The presence of homologous antiserum in the reaction sequence gave clearly visible, colored reactions on the membrane when 50 ul with approximately 10(5) or more cfu/ml were present. This new biotin-avidin microporous membrane (BAMM-ELISA) test can be used both to detect mycoplasmas and to speciate them. The BAMM-ELISA is simple, rapid, sensitive, specific and economical. As such, it has potential for aiding in the control of mycoplasma contamination in cell culture, and could prove useful in clinical diagnostic applications as well. |
In this article, the authors summarized the RT-ABCDE strategy for the management and prevention of human diseases, which includes ReTro—ABCDE (Examination regularity, Disease and risk factor control, Changing lifestyle and reducing pathways of infection and spread, Biochemical and Antagonistic index control and therapeutic treatment as well as RT—Routine and Right Treatment). The RT-ABCDE strategy, a novel concept and an essential method, should be a routine strategy for disease control and prevention. It should be proposed and applied in both clinical and preventive medicine. |
The global spread of emergent diseases is inevitably entangled with the structure of the population flows among different geographical regions. The airline transportation network in particular shrinks the geographical space by reducing travel time between the world's most populated areas and defines the main channels along which emergent diseases will spread. In this paper, we investigate the role of the large-scale properties of the airline transportation network in determining the global propagation pattern of emerging diseases. We put forward a stochastic computational framework for the modeling of the global spreading of infectious diseases that takes advantage of the complete International Air Transport Association 2002 database complemented with census population data. The model is analyzed by using for the first time an information theory approach that allows the quantitative characterization of the heterogeneity level and the predictability of the spreading pattern in presence of stochastic fluctuations. In particular we are able to assess the reliability of numerical forecast with respect to the intrinsic stochastic nature of the disease transmission and travel flows. The epidemic pattern predictability is quantitatively determined and traced back to the occurrence of epidemic pathways defining a backbone of dominant connections for the disease spreading. The presented results provide a general computational framework for the analysis of containment policies and risk forecast of global epidemic outbreaks. |
Objective: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. Design: Prospective case series. Setting: Walk-in medical clinic of a university hospital. Patients: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. Measurements and main results: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 3 34 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes.Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6–14.2),Moraxella catarrbalis (odds ratio 12.9, 95% confidence interval 3.1–79.5), andHemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2–7.4) were all associated with the presence of leukocytes. In contrast, nasophaiyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were “pathogenic” bacteria found. Conclusions: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis. |
Two studies are reported in this paper. The object of learning in both is the economic principle of changes in price as a function of changes in the relative magnitude of changes in demand and supply. The patterns of variation and invariance, defining the conditions compared were built into pedagogical tools (text, graphs, and worksheets). The first study is the latest in a series of studies aiming to test the fundamental conjecture of the Variation Theory of Learning that new meanings are acquired from experiencing differences against a background of sameness, rather than experiencing sameness against a background of differences. The study compares the learning outcomes under conditions consistent with the basic conjecture with the learning outcomes under conditions not consistent with the theory. The results support the conjecture. The second study shows, however, that the conditions that are consistent with the theory cannot be decided unless the learners’ pre-requisites for the task in question are taken into consideration. One set of the pedagogical tools was found to be highly effective for learners with a better initial grasp of the object of learning, while another set was found to be equally effective for learners with a weaker initial grasp of the object of learning. The two sets were equally ineffective when used for the “wrong” group of learners. |
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