title: Influenza treatment with neuraminidase inhibitors: Cost-effectiveness and cost-utility in healthy adults in the United Kingdom

text: We assessed the cost-effectiveness and cost-utility of treating influenza with neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer’s and societal perspective in the United Kingdom. A simulation model was developed to predict morbidity and mortality due to influenza and its specified complications, comparing neuraminidase inhibitors with usual care in an otherwise healthy adult population. Robustness of the results was tested by one-way and multiway as well as probabilistic sensitivity analyses. Treatment with either neuraminidase inhibitor results in reduced morbidity and faster return to normal activities. However, oseltamivir dominates zanamivir in cost-utility analysis due to its lower costs. Comparing oseltamivir with usual care, the costs are £14.36 per day of normal activity gained and £5,600 per quality-adjusted life-year gained from the healthcare payer perspective. Oseltamivir dominates usual care from the societal perspective. Treatment with oseltamivir is a cost-effective strategy for otherwise healthy adults in the UK from both the healthcare payer and societal perspective.


title: Infections gastro-intestinales chez le patient immunocompromis

text: The gastrointestinal tract is frequently involved in immunocompromised hosts. The most common digestive manifestations are dysphagia, odynophagia and diarrhea. These diseases are more frequent in patients with acquired immunodeficiency virus (AIDS). These GI diseases are of several categories: HIV related inflammatory conditions (HIV related enteropathy, idiopathic esophageal ulceration), infections due to germs also commonly present in immunocompetent patients (Salmonellosis, shigellosis,…), opportunistic infections (CMV, Mucormycosis,Cryptosporidium, Mycobacterium, Isospora belli,…). The prevalence, pathogenesis, clinical manifestation, gross pathological findings and microscopic features are discussed for each entity.


title: Unilateral cervical vagotomy decreases the magnitude of neurogenic inflammation induced by capsaicin in the ipsilateral bronchial tree of rats

text: Electrical stimulation of a single cervical vagus nerve produces neurogenic inflammation on the stimulated side of the bronchial tree, including the first (main) to the 4th order bronchi. In the contralateral bronchial tree, in contrast, only the proximal part of the main bronchus exhibits inflammatory changes, suggesting that vagal sensory axons present in the bronchi largely originate from the ipsilateral vagus nerve. Intravenous administration of capsaicin can evoke neurogenic inflammation in bilateral bronchial trees. Sensory axons from various sources are thought to be stimulated by this irritant. The extent to which neurogenic inflammation in both bronchial trees might be reduced by unilateral vagotomy is not known. In the present study, we sought to characterize the effect of unilateral cervical vagotomy on capsaicin-induced changes in plasma extravasation and secretory activity of goblet cells in the bronchial trees of both sides. To quantify the magnitude of neurogenic plasma extravasation, Evans blue was used as a tracer dye to measure spectrophotometrically its amount in the bronchial wall. Another tracer dye, Monastral blue, was used to localize the distribution of leaky blood vessels and to measure morphometrically their area density in the whole mounts. To investigate cell and tissue responses of the mucosa, histological methods were employed. After 2 or 4 postoperative weeks, the rats were intravenously administered with a single dose of capsaicin, 150 μg/kg. This resulted in different magnitudes of Evans blue extravasation in the bronchi of the two sides in vagotomized rats. Extravasation of Evans blue dye in the bronchial tree ipsilateral to vagotomy was one-half to two-thirds of that of the contralateral bronchial tree. For the distal region of the main stem bronchus, the area density of Monastral blue-labeled blood vessels in the operated side was one-half of that in the unoperated side, and for the secondary bronchus, the area density of these blood vessels in the operated side was one-quarter of that in the unoperated side. Histological study indicated that in the bronchial mucosa ipsilateral to vagotomy edematous change was not obvious, and most goblet cells were not responsive to stimulation by capsaicin, in contrast to the contralateral side where edematous change was very prominent and goblet cells were very sensitive to capsaicin. It is concluded that unilateral cervical vagotomy could selectively desensitize the mucosa of the ipsilateral bronchial tree to capsaicin, and therefore, decrease the magnitude of neurogenic inflammation.


title: Biophysical studies of a ruthenium(II) polypyridyl complex binding to DNA and RNA prove that nucleic acid structure has significant effects on binding behaviors

text: The interactions of a metal complex [Ru(phen)(2)PMIP](2+) {Ru=ruthenium, phen=1,10-phenanthroline, PMIP=2-(4-methylphenyl)imidazo[4,5-f]1,10-phenanthroline} with yeast tRNA and calf thymus DNA (CT DNA) have been investigated comparatively by UV-vis spectroscopy, fluorescence spectroscopy, viscosity measurements, isothermal titration calorimetry (ITC), as well as equilibrium dialysis and circular dichroism (CD). Spectroscopic studies together with ITC and viscosity measurements indicate that both binding modes of the Ru(II) polypyridyl complex to yeast tRNA and CT DNA are intercalation and yeast tRNA binding of the complex is stronger than CT DNA binding. ITC experiments show that the interaction of the complex with yeast tRNA is driven by a moderately favorable enthalpy decrease in combination with a moderately favorable entropy increase, while the binding of the complex to CT DNA is driven by a large favorable enthalpy decrease with a less favorable entropy increase. The results from equilibrium dialysis and CD suggest that both interactions are enantioselective and the Δ enantiomer of the complex may bind more favorably to both yeast tRNA and CT DNA than the Λ enantiomer does, and that the complex is a better candidate for an enantioselective binder to yeast tRNA than to CT DNA. Taken together, these results indicate that the structures of nucleic acids have significant effects on the binding behaviors of metal complexes.


title: Influence of the relA gene on ribosome frameshifting

text: We have examined the influence of genotype at the relA locus on the kinetics of leftward (or –1) frameshifting at a variety of codons calling for a limiting aminoacyl-tRNA species. We used lacZ left-frameshift reporter constructs carrying the sequence U UUC xyz, where xyz was each of three triplets coding for three different amino acids; we slowed the ribosomes at each of these by limiting for the amino acid or for the aminoacyl-tRNA. In all cases, limitation stimulated leftward frameshifting. In all cases, the stimulation was greater in relA mutant cells than in their wild-type relA (+) counterparts. In the latter genotype, the increased frameshifting was constant from the start of the limitation regime. This was also true of the relA mutant strain during limitation for lysine-tRNA or for leucine; however, during limitation for isoleucine-tRNA (or for isoleucine) the mutant showed a gradual, progressive increase in frameshifting, suggesting an indirect effect. We suggest that gradual accumulation of undermodified tRNAs, which is characteristic of the relA response, is involved. However, the specific modification involved is unknown. It is not queosine: analysis of a tgt mutant that is completely defective in queosine modification showed no increase in leftward frameshifting on the reporter which showed the larger, gradual increase during the relA response to isoleucine-tRNA limitation.


title: Simultaneous Determination of Four Active Components in Tobacco Wastes by LC

text: A liquid chromatographic method was developed for the simultaneous quantification of four major active components in tobacco (Nicotiana tobaccum L.) wastes. Samples were extracted with 70% v/v aqueous methanol, four compounds including chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid and caffeic acid were identified and determined by using LC coupled to electrospray tandem mass spectrometry and LC–UV method, respectively. Separation in LC–UV was on an Alltima C(18) column (250 mm × 4.6 mm i.d.; 5 μm) with a mobile phase consisting acetonitrile: ammonium acetate buffer (pH 4.5) (5:95 v/v), at a flow rate of 1.0 mL min(−1), detected at 327 nm. Four regression equations showed good linear relationships (r (2) > 0.999) between the peak area of each marker and concentration. The method has good repeatability and precision, the intra-day and inter-day RSD for both retention time and peak area was less than 1.0%. The recoveries, measured at three concentration levels, varied from 96.33 to 101.10%. The LOD (S/N = 3) and LOQ (S/N = 6) were less than 0.010 and 0.795 μg·mL(−1), respectively. This assay was successfully applied to the determination of four active compounds in ten samples. The results indicated that the developed assay method was rapid, accurate, reliable and could be readily utilized as a quantitative analysis method for various of tobacco wastes.


title: Globule leukocytes and mast cells in the rat trachea: their number, distribution, and response to compound 48/80 and dexamethasone

text: Globule leukocytes in the epithelium of the rat trachea may be counterparts of mucosal mast cells that are located in the gastrointestinal tract. If they are indeed similar to mucosal mast cells, globule leukocytes would be expected to decrease in number in rats treated with dexamethasone but not in rats treated with compound 48/80, an agent which causes non-antigenic degranulation of connective tissue mast cells. In this study, we determined the number and compared the distribution of globule leukocytes and connective tissue mast cells in the tracheas of pathogen-free rats. We then determined whether the number of these two types of cells changes in rats treated for 5 days with compound 48/80, dexamethasone, a combination of compound 48/80 and dexamethasone, or saline. We identified globule leukocytes and mast cells in whole mounts and histological sections of rat tracheas by using a histochemical reaction that demonstrates the chymotrypsin-like protease (chloroacetate esterase) present in mast cell granules. Using this method, we found that aproximately 225000 globule leukocytes were present in the epithelium of the trachea. These cells were most abundant in the rostral trachea. Rats treated with dexamethasone had a 91% reduction in the number of globule leukocytes with protease-containing granules, but rats treated with compound 48/80 had a normal number of these cells. We found some 55000 connective tissue mast cells in the same tracheas. Mast cells were most abundant in the posterior membrane of the caudal trachea and in the lamina propria between cartilaginous rings. Rats treated with compound 48/80 had a 96% reduction in mast cells with protease-containing granules, but rats treated with dexamethasone had a normal complement of mast cells. We conclude that globule leukocytes are abundant in the tracheas of healthy rats, are similar in morphology and pharmacological responses to mucosal mast cells located in other organs of rats, and are more numerous than and have a different distribution than connective tissue mast cells. Globule leukocytes in the tracheal epithelium may have a role in respiratory defenses similar to that of mucosal mast cells in other organs.


Coronavirus-like particles andCampylobacter in marmosets with diarrhea and colitis


title: Effect of monensin on the Golgi apparatus of absorptive cells in the small intestine of the rat: Morphological and cytochemical studies

text: The effect of short-time treatment with the ionophore monensin, administered intraluminally at concentrations of 5 and 10 μM, was studied on the Golgi apparatus of absorptive cells in the small intestine of the rat. At 2–3 min after treatment most of the Golgi stacks exhibited dilated cisternae. At 4–5 min stacked cisternae were absent; they were replaced by groups of smooth-surfaced vacuoles. Dilatation and vacuolization occurred in the entire stacks without preferential effect on any particular Golgi subcompartment. Monensin did not influence the cytochemical Golgi reaction of thiamine pyrophosphatase and acid phosphatase. The characteristic staining pattern of these two enzymes in all Golgi cisternae of absorptive cells in the proximal small intestine, and the reactivity restricted to trans cisternae in distal segments of the small intestine, were unchanged after treatment with monensin. In the distal small intestine, the cytochemical pattern allowed the monensin-induced vacuoles to be attributed to the former cisor trans-Golgi face. Further, the cytochemical results demonstrate that vacuolization is not restricted to the stacked cisternae, but includes the trans-most cisterna. The latter, usually located at some distance from the Golgi stacks, has been defined as belonging to the GERL system in several types of cells. The clear response to monensin, an agent that selectively affects the Golgi apparatus, indicates common properties between trans-most and stacked Golgi cisternae.


title: Using Survey Results Regarding Hepatitis B Knowledge, Community Awareness and Testing Behavior Among Asians to Improve the San Francisco Hep B Free Campaign

text: Asians are disproportionately affected by chronic hepatitis B (HBV) infection and its fatal consequences. The Hep B Free campaign was launched to eliminate HBV in San Francisco by increasing awareness, testing, vaccination and linkage to care. The campaign conducted 306 street intercept and telephone interviews of San Francisco Asians to assess current levels of HBV knowledge, testing behaviors and effectiveness of existing campaign media materials. One-third of respondents ranked HBV as a key health issue in the Asian community, second to diabetes. General HBV awareness is high (85%); however, a majority could not name an effective prevention method. Sixty percent reported having been tested for HBV; provider recommendation was the most often cited reason for testing. Respondents reported a high level of trust in their providers to correctly assess which health issues they may be at risk for developing and test accordingly, confirming that efforts to increase HBV testing among Asians must simultaneously mobilize the public to request testing and compel providers to test high-risk patients. Regarding community awareness, more than half reported hearing more about HBV recently; younger respondents were more likely to have encountered campaign materials and recall correct HBV facts. Assessment of specific campaign materials found that while upbeat images and taglines captured attention and destigmatized HBV, messages that emphasize the pervasiveness and deadly consequence of infection were more likely to drive respondents to seek education and testing. The campaign used survey results to focus efforts on more intensive provider outreach and to create messages for a new public outreach media campaign.


title: Optofluidic integration for microanalysis

text: This review describes recent research in the application of optical techniques to microfluidic systems for chemical and biochemical analysis. The “lab-on-a-chip” presents great benefits in terms of reagent and sample consumption, speed, precision, and automation of analysis, and thus cost and ease of use, resulting in rapidly escalating adoption of microfluidic approaches. The use of light for detection of particles and chemical species within these systems is widespread because of the sensitivity and specificity which can be achieved, and optical trapping, manipulation and sorting of particles show significant benefits in terms of discrimination and reconfigurability. Nonetheless, the full integration of optical functions within microfluidic chips is in its infancy, and this review aims to highlight approaches, which may contribute to further miniaturisation and integration.


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title: Summarizing the Evidence on the International Trade in Illegal Wildlife

text: The global trade in illegal wildlife is a multi-billion dollar industry that threatens biodiversity and acts as a potential avenue for invasive species and disease spread. Despite the broad-sweeping implications of illegal wildlife sales, scientists have yet to describe the scope and scale of the trade. Here, we provide the most thorough and current description of the illegal wildlife trade using 12 years of seizure records compiled by TRAFFIC, the wildlife trade monitoring network. These records comprise 967 seizures including massive quantities of ivory, tiger skins, live reptiles, and other endangered wildlife and wildlife products. Most seizures originate in Southeast Asia, a recently identified hotspot for future emerging infectious diseases. To date, regulation and enforcement have been insufficient to effectively control the global trade in illegal wildlife at national and international scales. Effective control will require a multi-pronged approach including community-scale education and empowering local people to value wildlife, coordinated international regulation, and a greater allocation of national resources to on-the-ground enforcement.


title: Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases

text: In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.


Identic viral infections in four cases of malignant lymphoepithelioma


title: Biowarfare as a biopolitical icon

text: Nuclear warfare threat has been one of the main driver for cultural, political, economical and social changes in the late twentieth century, biological warfare threat is about to take it over. However, while nuclear warfare was a concrete possibility, biological warfare is just an elusive risk. This paper will explore some reasons for this apparent inconsistency by discussing biowarfare from a symbolic point of view, looking for its inner meanings and philosophical implications.


title: Balkan endemic nephropathy in Vratza, Bulgaria, 1964–1987: An epidemiologic analysis of population-based disease registers

text: Balkan Endemic Nephropathy (BEN), first described in 1956 in Vratza region, Bulgaria, may result from prolonged, chronic exposure to environmental toxicants, but the underlying etiologic factors remain elusive. There has been no recent systematic characterization of the epidemiology of this disease. Recently, it has been suggested that the incidence of the disease is decreasing. We therefore abstracted data from registers of patients in 21 affected villages and the town of Vratza, Bulgaria maintained from 1964 through 1987. In 1964, the prevalence of BEN was 6.0 per 1000 inhabitants; among residents of the affected villages, the prevalence was 12.3 per 1000. From 1965 to 1975 the incidence rate was 0.7 per 1000 person-years, and from 1976 to 1987 the incidence rate was 0.3 per 1000 person-years (rate ratio 0.43; p < 0.001). Incidence was much lower in Vratza town; among residents of affected villages, the period-specific rates were 1.7 and 0.8 per 1000 per year, respectively (rate ratio 0.47; p < 0.01). These trends were consistent across all villages for which registers were maintained. Median survival following registration increased from 2.0 to 5.0 years over the same period (p < 0.001). BEN appears to be decreasing in incidence in this region.


title: Traveling Waves in Spatial SIRS Models

text: We study traveling wavefront solutions for two reaction–diffusion systems, which are derived respectively as diffusion approximations to two nonlocal spatial SIRS models. These solutions characterize the propagating progress and speed of the spatial spread of underlying epidemic waves. For the first diffusion system, we find a lower bound for wave speeds and prove that the traveling waves exist for all speeds bigger than this bound. For the second diffusion system, we find the minimal wave speed and show that the traveling waves exist for all speeds bigger than or equal to the minimal speed. We further prove the uniqueness (up to translation) of these solutions for sufficiently large wave speeds. The existence of these solutions are proved by a shooting argument combining with LaSalle’s invariance principle, and their uniqueness by a geometric singular perturbation argument.


title: Five myths about AIDS that have misdirected research and treatment

text: A number of widely repeated and factually incorrect myths have pervaded the AIDS research literature, misdirecting research and treatment. Five of the most outstanding are: 1) that all risk groups develop AIDS at the same rate following HIV infection; 2) that there are no true seroreversions following HIV infection; 3) that antibody is protective against HIV infection; 4) that the only way to treat AIDS effectively is through retroviral therapies; and 5) that since HIV is so highly correlated with AIDS incidence, it must be the sole necessary and sufficient cause of AIDS. A huge body of research, reviewed in this paper, demonstrates the falsity of these myths. 1) The average number of years between HIV infection and AIDS is greater than 20 years for mild hemophiliacs, 14 years for transfussion severe hemophiliacs, 10 years for old severe hemophiliacs, 10 years for homosexual men, 6 years for transfusion patients of all ages, 2 years for transplant patients, and 6 months for perinatally infected infants. These differences can only be explained in terms of risk-group associated cofactors. 2) Seroreversions are common. Between 10 and 20 percent of HIV-seronegative people in high risk groups have T-cell immunity to HIV, and may have had one or more verified positive HIV antibody tests in the past. 3) Antibody, far from being protective against HIV, appears to be highly diagnostic of loss of immune regulation of HIV, and some evidence of antibody-enhancement of infection exists. 4) Non-retroviral treatments of HIV infection, including safer sex practices, elimination of drug use, high nutrient diets, and limited reexposure to HIV and its cofactors have proven to be effective means of preventing or delaying onset of AIDS. 5) Many immunosuppressive factors, including drug use, multiple concurrent infections, and exposure to alloantigens, are as highly correlated with AIDS risk groups as HIV. These data are more consistent with AIDS being a multifactorial or synergistic disease than a monofactorial one.


title: Epidemiological survey on bacterial, viral and parasitic agents in patients affected by acute enteritis

text: During the period June 1983 – May 1984, faecal specimens from 797 patients with acute enteritis were examined for the presence of bacterial, viral and parasitic agents; 209 (26.2%) enteritic pathogens were identified, of whom 118 (35.4%) in 333 samples from the pediatrics wards. Bacterial agents were detected in 122 (15.3%), viruses in 63 (7.9%) and parasites in 25 (3.1%) of the 797 specimens. LT-producing E. coli, Salmonella and Rotavirus were the most frequent pathogens. Bacterial agents occurred most frequently in the summer and autumnal months, whereas viruses showed two peaks, the first one in summer due to cultivable agents, the second in winter to Rotavirus mainly.


title: Microfluidic devices harboring unsealed reactors for real-time isothermal helicase-dependent amplification

text: High-throughput microchip devices used for nucleic-acid amplification require sealed reactors. This is to prevent evaporative loss of the amplification mixture and cross-contamination, which may occur among fluidically connected reactors. In most high-throughput nucleic-acid amplification devices, reactor sealing is achieved by microvalves. Additionally, these devices require micropumps to distribute amplification mixture into an array of reactors, thereby increasing the device cost, and adding complexity to the chip fabrication and operation processes. To overcome these limitations, we report microfluidic devices harboring open (unsealed) reactors in conjunction with a single-step capillary based flow scheme for sequential distribution of amplification mixture into an array of reactors. Concern about evaporative loss in unsealed reactors have been addressed by optimized reactor design, smooth internal reactor surfaces, and incorporation of a localized heating scheme for the reactors, in which isothermal, real-time helicase-dependent amplification (HDA) was performed.


Prospects for effective non-antimicrobial antidiarrheal agents


title: Integrating food security into public health and provincial government departments in British Columbia, Canada

text: Food security policy, programs, and infrastructure have been incorporated into Public Health and other areas of the Provincial Government in British Columbia, including the adoption of food security as a Public Health Core Program. A policy analysis of the integration into Public Health is completed by merging findings from 48 key informant interviews conducted with government, civil society, and food supply chain representatives involved in the initiatives along with relevant documents and participant/direct observations. The paper then examines the results within the context of historic and international trends and theoretical models of food policy, community food security, and applied policy research. Public Health re-emerged as a driver of food security in BC—both as a key player and in positing the public’s health as a driver in food security and food systems. While Public Health’s lead role supported an increase in legitimacy for food security in BC, interviewees described a clash of cultures between Public Health and civil society. The clash of cultures occurred partly as a result of Public Health’s limited food security mandate and top down approach. Consequently civil society voice at the provincial level was marginalized. A social policy movement toward a new political paradigm—regulatory pluralism—calls for greater engagement of civil society, and for all sectors to work together toward common goals. A new, emerging policy map is proposed for analyzing the dynamics of food security and health promotion initiatives in BC.


Interferons and viral infections


title: The Economic Case for a Pandemic Fund

text: The rapid urban spread of Ebola virus in West Africa in 2014 and consequent breakdown of control measures led to a significant economic impact as well as the burden on public health and wellbeing. The US government appropriated $5.4 Billion for FY2015 and WHO proposed a $100 Million emergency fund largely to curtail the threat of future outbreaks. Using epidemiological analyses and economic modeling, we propose that the best use of these and similar funds would be to serve as global insurance against the continued threat of emerging infectious diseases. An effective strategy would involve the initial investment in strengthening mobile and adaptable capacity to deal with the threat and reality of disease emergence, coupled with repeated investment to maintain what is effectively a ‘national guard’ for pandemic prevention and response. This investment would create a capital stock that could also provide access to safe treatment during and between crises in developing countries, lowering risk to developed countries.


title: Mutation of a highly conserved base in the yeast mitochondrial 21S rRNA restricts ribosomal frameshifting

text: A mutation shown to cause resistance to chloramphenicol inSaccharomyces cerevisiae was mapped to the central loop in domain V of the yeast mitochondrial 21S rRNA. The mutant 21S rRNA has a base pair exchange from U(2677) (corresponding to U(2504) inEscherichia coli) to C(2677), which significantly reduces rightward frameshifting at a UU UUU UCC A site in a + 1 U mutant. There is evidence to suggest that this reduction also applies to leftward frameshifting at the same site in a − 1 U mutant. The mutation did not increase the rate of misreading of a number of mitochondrial missense, nonsense or frameshift (of both signs) mutations, and did not adversely affect the synthesis of wild-type mitochondrial gene products. It is suggested here that ribosomes bearing either the C(2677) mutation or its wild-type allele may behave identically during normal decoding and only differ at sites where a ribosomal stall, by permitting non-standard decoding, differentially affects the normal interaction of tRNAs with the chloramphenicol resistant domain V. Chloramphenicol-resistant mutations mapping at two other sites in domain V are described. These mutations had no effect on frameshifting.


title: Mechanism of Preferential Packaging of Negative Sense Genomic RNA by Viral Nucleoproteins in Crimean-Congo Hemorrhagic Fever Virus

text: The Crimean-Congo Hemorrhagic Fever (CCHF) is an infectious disease of high virulence and mortality caused by a negative sense RNA nairovirus. The genomic RNA of CCHFV is enwrapped by its nucleoprotein. Positively charged residues on CCHFV nucleoprotein provide multiple binding sites to facilitate genomic RNA encapsidation. In the present work, we investigated the mechanism underlying preferential packaging of the negative sense genomic RNA by CCHFV nucleoprotein in the presence of host cell RNAs during viral assembly. The work included genome sequence analyses for different families of negative and positive sense RNA viruses, using serial docking experiments and molecular dynamic simulations. Our results indicated that the main determinant parameter of the nucleoprotein binding affinity for negative sense RNA is the ratio of purine/pyrimidine in the RNA molecule. A negative sense RNA with a purine/pyrimidine ratio (>1) higher than that of a positive sense RNA (<1) exhibits higher affinity for the nucleoprotein. Our calculations revealed that a negative sense RNA expresses about 0.5 kJ/mol higher binding energy per nucleotide compared to a positive sense RNA. This energy difference produces a binding energy high enough to make the negative sense RNA, the preferred substrate for packaging by CCHFV nucleoprotein in the presence of cellular or complementary positive sense RNAs. The outcome of this study may contribute to ongoing researches on other viral diseases caused by negative sense RNA viruses such as Ebola virus which poses a security threat to all humanity.


title: Expression of Helicobacter pylori urease subunit B gene in transgenic rice

text: Helicobacter pylori ureB antigen gene was cloned to the 5′-end of gus (β-glucuronidase) reporter gene between CaMV35S promoter and the octopine synthase (OCS) terminator in the plasmid, pCAMBIA13011. It was then introduced into rice genome by Agrobacterium-mediated transformation. A total of 30 regenerated plants with hygromycin resistance were obtained in the selection media. The putative transgenic individuals were tested for the presence of ureB in the nuclear genome of rice plants by PCR analysis. Expression of ureB gene in rice plants was verified by RT-PCR and Western blot analysis using polyclonal human antiserum for transcription and translation levels respectively. These results provide a basis for further studies on the accumulation level of UreB recombinant protein in transgenic rice and potential utilization of transgenic rice for delivery of edible vaccines against Helicobacter pylori.


title: Host Biology and Anthropogenic Factors Affect Hepadnavirus Infection in a Neotropical Bat

text: The tent-making bat hepatitis B virus (TBHBV) is a hepadnavirus closely related to human hepatitis B virus. The ecology of TBHBV is unclear. We show that it is widespread and highly diversified in Peters’ tent-making bats (Uroderma bilobatum) within Panama, while local prevalence varied significantly between sample sites, ranging from 0 to 14.3%. Females showed significantly higher prevalence than males, and pregnant females were more often acutely infected than non-reproductive ones. The distribution of TBHBV in bats was significantly affected by forest cover, with higher infection rates in areas with lower forest cover. Our data indicate that loss of natural habitat may lead to positive feedback on the biotic factors driving infection possibility. These results underline the necessity of multidisciplinary studies for a better understanding of mechanisms in pathogen–host relationships and for predictions in disease ecology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-018-1387-5) contains supplementary material, which is available to authorized users.


title: Biological Invasions Across Spatial Scales: Intercontinental, Regional, and Local Dispersal of Cladoceran Zooplankton

text: The frequency of dispersal of invertebrates among lakes depends upon perspective and spatial scale. Effective passive dispersal requires both the transport of propagules and the establishment of populations large enough to be detected. At a global scale, biogeographic patterns of cladoceran zooplankton species suggest that effective dispersal among continents was originally rare, but greatly increased in the past century with expanded commerce. Genetic analysis allows some reconstruction of past dispersal events. Allozyme and mitochondrial DNA comparisons among New World and Old-World populations of several exotic cladocerans have provided estimates for likely source populations of colonists, their dispersal corridors, and timing of earlier dispersal events. Detecting the Old-World tropical exotic Daphnia lumholtzi early in its invasion of North America has allowed detailed analysis of its spatial spread. Twelve years of collection records indicate a rapid invasion of reservoirs in the United States, by both regional spread and long-distance jumps to new regions. Combining landscape features with zooplankton surveys from south-central US reservoirs revealed higher colonization rates of D. lumholtzi at lower landscape positions, a result which can be explained by either greater propagule load or by higher susceptibility of these downstream reservoirs. Because invaded reservoirs provide a source of propagules for nearby floodplain ponds, the rarity of this species in ponds suggests limitation by local environments. Such analyses of invading species over multiple spatial scales allow a better understanding of ecological processes governing invasion dynamics.


title: Persistent intrathecal secretion of oligoclonal, Borrelia burgdorferi-specific IgG in chronic meningoradiculomyelitis

text: In the cerebrospinal fluid IgG of five patients with lymphomeningoradiculitis (Bannwarth's syndrome) and radiculomyelitis studied by immunoblot technique an oligoclonal pattern was found. Most of these oligoclonal bands were specific for Borrelia burgdorferi. In patients suffering from chronic meningoradiculomyelitis, repeated CSF examination by this technique showed persistent secretion of identical IgG bands. Thus, the specific humoral immune response and the disease activity could be documented over the course of the disease.


title: Low prevalence of Chlamydia pneumoniae and Mycoplasma pneumoniaeamong patients with symptoms of respiratory tract infections inDutch general practices

text: Acute respiratory disease is one of the most common reasons to consult a general practitioner. A substantial part of these diseases cannot be explained by an infection with a virus or a common pathogenic bacterium. To study this diagnostic deficit, the prevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae infections was determined in two groups of patients consulting a general practitioner. DNA of C. pneumoniae and M. pneumoniae was detected by a polymerase chain reaction (PCR) in nose/throat swabs from six (1.1%), and from seven (1.3%) patients, respectively, of 557 patients consulting a general practitioner for complaints suggestive for a virus infection during the 1994/1995 respiratory infections season. Two patients remained C. pneumoniae PCR-positive for at least 4 weeks. All others were negative within 3 weeks. Double infections of C. pneumoniae and influenza virus (3/6), and of M. pneumoniae and respiratory syncytial virus (1/7) or rhinovirus (1/7) were diagnosed. During the 1992/1993 season, attempts to isolate C. pneumoniae in cell culture or to detect C. pneumoniae DNA by PCR using throat swabs were all negative for 80 patients with a sore throat, although serological data suggested a C. pneumoniae infection in 13 (16%) patients. A specimen from another patient of this group was M. pneumoniae PCR-positive and the corresponding serum specimens showed a persistent high antibody titre. In summary, the prevalence of acute C. pneumoniae and M. pneumoniae infections was less than 2% in patients consulting a general practitioner.


title: Needlestick injuries among health care workers: Occupational hazard or avoidable hazard?

text: OBJECTIVES: The objective of this study was to describe the mechanisms and preventability of occupational percutaneous blood exposure of healthcare workers through needlestick injuries and to discuss rational strategies for prevention. METHODS: To calculate the preventability, we surveyed in a first step the number and kind of needlestick injuries and in a second step the reasons for the injuries and the working conditions of the healthcare workers. Both data sets were collected in independent anonymous questionnaire covering occupational blood exposure among healthcare workers in a German university hospital. RESULTS: Needlestick injuries were caused through unsafe procedures, difficult working conditions and unsafe devices. On average, 50.3% (n = 492/978) of all needlestick injuries could have been avoided by the use of safety devices, whereas only 15.2% could have been prevented by organizational measures. In our study, 31.5% (n = 503/1598) of participant healthcare workers had sustained at least one needlestick injury in the past twelve months. The rate of underreporting was about 75%. After introduction of safety devices, 91.8% of the healthcare workers reported being satisfied with the anti-needlestick devices and 83.4% believed that safety devices would increase the safety of the work environment. CONCLUSIONS: Occupational exposure to blood is a common problem among healthcare workers. The introduction of safety devises is one of the main starting points for avoidance of needlestick injuries, and acceptance among healthcare workers is high. Further targets for preventive measures, such as training in safe working routines, are necessary for improvement of safe work conditions.


title: Effect of exogenous mouse interferon on murine fulminant hepatitis induced by mouse hepatitis virus type 2

text: We investigated the effect of exogenous mouse α-+β-interferon produced by mouse L cells on the growth of mouse hepatitis virus type 2 (MHV-2) in the liver, the development of liver cell necrosis, and survival in murine fulminant hepatitis induced by MHV-2. Murine fulminant hepatitis was induced in 4-week-old male ICR mice by intraperitoneal inoculation of MHV-2. Mouse interferon (10(3) IU/mouse/day) was intraperitoneally injected every day. Exogenous mouse interferon suppressed both the growth of MHV-2 in the liver tissue and development of liver cell necrosis, and prolonged the survival. It was also found that the earlier mouse interferon was administered, the greater was the prolongation of survival.


title: Synthesis of Organotin Polyamine Ethers Containing Acyclovir and their Preliminary Anticancer and Antiviral Activity

text: Organotin polyamine ethers containing acyclovir in their backbone were synthesized in moderate to high yield employing the aqueous interfacial polycondensation system. The products are high molecular weight polymers. Infrared spectroscopy of the products shows new bands characteristic of the formation of Sn–N and Sn–O bonds consistent with the proposed structure. MALDI-TOF MS below 2000 Da shows the presence of organotin and acyclovir units containing these two moieties. The products show moderate inhibition of a number of cancer cell lines and exhibit the ability to inhibit a number of viruses, particularly the herpes simplex virus-1 and varicella zoster virus that are responsible for herpes, chicken pox and shingles.


title: Characteristics of airborne Staphylococcus aureus (including MRSA) in Chinese public buildings

text: The aim of this study was to evaluate the concentration and size distribution of airborne culturable Staphylococcus aureus (S. aureus) (including MRSA) in Chinese public buildings. Air samples were collected, using six-stage Andersen sampler from five different public buildings in one large Chinese community. The mean indoor concentrations of the total and respirable airborne S. aureus were 72 and 50 CFU/m(3) in the general hospital, 72 and 49 CFU/m(3) in the kindergarten, 76 and 52 CFU/m(3) in the hotel, 84 and 57 CFU/m(3) in the movie theater, and 55 and 40 CFU/m(3) in the university classroom. Respirable S. aureus amounted to approximately 57–73 % of the total S. aureus concentrations. Mean total and respirable concentrations of airborne MRSA were 32 and 20 CFU/m(3) in the general hospital, 20 and 13 CFU/m(3) in the kindergarten, 23 and 16 CFU/m(3) in the hotel, 33 and 20 CFU/m(3) in the movie theater, and 24 and 17 CFU/m(3) in the university classroom. Respirable MRSA amounted to approximately 61–72 % of the total MRSA concentrations. The ratios of indoor and outdoor concentration for airborne S. aureus and MRSA were more than 1.0 in all the investigated public buildings. The size distribution results showed relatively high collection rates on stage 4 (2.1–3.3 μm) for both airborne culturable S. aureus and MRSA regardless of the type of public buildings.


title: Cleavage mechanism of the H5N1 hemagglutinin by trypsin and furin

text: The cleavage property of hemagglutinin (HA) by different proteases was the prime determinant for influenza A virus pathogenicity. In order to understand the cleavage mechanism, molecular modeling tools were utilized to study the coupled model systems of the proteases, i.e., trypsin and furin and peptides of the cleavage sites specific to H5N1 and H1 HAs, which constitute models of HA precursor in complex with cleavage proteases. The peptide segments ‘RERRRKKR ↓ G’ and ‘SIQSR ↓ G’ from the high pathogenic H5N1 H5 and the low pathogenic H1N1 H1 cleavage sites were docking to the trypsin and furin active pockets, respectively. It was observed through the docking studies that trypsin was able to recognize and cleave both the high pathogenic and low pathogenic hemagglutinin, while furin could only cleave the high pathogenic hemagglutinin. An analysis of binding energies indicated that furin got most of its selectivity due to the interactions with P(1), P(4), and P(6), while having less interaction with P(2) and little interactions with P(3), P(5), P(7), and P(8). Some mutations of H5N1 H5 cleavage sequence fitted less well into furin and would reduce high pathogenicity of the virus. These findings hint that we should focus at the subsites P(1), P(4), and P(6) for developing drugs against H5N1 viruses.


title: Coexistence of free-living amoebae and bacteria in selected South African hospital water distribution systems

text: Pathogenic free-living amoebae (FLA), such as Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba species isolated from aquatic environments have been implicated in central nervous system, eye and skin human infections. They also allow the survival, growth and transmission of bacteria such as Legionella, Mycobacteria and Vibrio species in water systems. The purpose of this study was to investigate the co-occurrence of potentially pathogenic FLA and their associated bacteria in hospital water networks in Johannesburg, South Africa. A total of 178 water (n = 95) and swab (n = 83) samples were collected from two hospital water distribution systems. FLA were isolated using the amoebal enrichment technique and identified using PCR and 18S rDNA sequencing. Amoebae potentially containing intra-amoebal bacteria were lysed and cultured on blood agar plates. Bacterial isolates were characterized using the VITEK®2 compact System. Free-living amoebae were isolated from 77 (43.3 %) of the samples. Using microscopy, PCR and 18S rRNA sequencing, Acanthamoeba spp. (T3 and T20 genotypes), Vermamoeba vermiformis and Naegleria gruberi specie were identified. The Acanthamoeba T3 and T20 genotypes have been implicated in eye and central nervous system infections. The most commonly detected bacterial species were Serratia marcescens, Stenotrophomonas maltophilia, Delftia acidovorans, Sphingomonas paucimobilis and Comamonas testosteroni. These nosocomial pathogenic bacteria are associated with systematic blood, respiratory tract, the urinary tract, surgical wounds and soft tissues infections. The detection of FLA and their associated opportunistic bacteria in the hospital water systems point out to a potential health risk to immune-compromised individuals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00436-016-5271-3) contains supplementary material, which is available to authorized users.


S. 1966 Global Child Survival Act of 2009: Analysis and Recommendations


title: Psychological Predictors of Health Anxiety in Response to the Zika Virus

text: The threat of a United States (U.S.) Zika virus pandemic during 2015–2016 was associated with public anxiety. Such threats represent opportunities to examine hypotheses about health anxiety. The present study investigated psychological predictors of Zika-related anxiety during the 2015–2016 outbreak. U.S. adults (N = 216) completed a battery of measures assessing Zika-related anxiety as well as psychological variables hypothesized to predict anxious responding to the threat of a domestic Zika outbreak. Contrary to hypotheses, regression analyses indicated that only contamination severity overestimates and greater Zika knowledge significantly predicted Zika-related anxiety. Study limitations and clinical implications are discussed.


title: The Short Health Anxiety Inventory: Psychometric Properties and Construct Validity in a Non-clinical Sample

text: Contemporary conceptualizations of hypochondriasis (HC) as severe health anxiety have led to the development of cognitive-behavioral approaches to understanding, assessing, and treating this problem. The Short Health Anxiety Inventory (SHAI) is a new instrument that measures cognitive factors associated with HC. In the present study, we examined the psychometric properties and factor structure of the SHAI in a large sample of medically healthy university students. We also examined the scale’s convergent, divergent, and predictive validity. Results indicated that the SHAI has good psychometric properties and contains three factors that assess the perceived likelihood and perceived severity of becoming ill, and body vigilance. Facets of health anxiety uniquely predicted increased safety-seeking behavior and medical utilization, behaviors that are commonly observed in HC. Results are discussed in terms of the cognitive-behavioral model of HC.


Ninth Meeting of the European Neurological Society 5–9 June, 1999, Milan, Italy: Abstracts of Symposia, Free Communications and Posters


title: Viral antibodies in multiple sclerosis

text: The sera of 176 MS patients and of 150 healthy adult controls were assayed for antibodies against mumps, rubella, Sendai and herpes simplex viruses, a higher prevalence of measles c.f.a. having already been demonstrated in the MS patients. The CSF of 48 of the MS patients were subjected to the same tests. The patients differed from the controls in a higher prevalence of h.i.a. to mumps and of c.f.a. to herpes simplex. For the latter, but not for the former, the prevalence was statistically higher only in patients treated with immunosuppressants. To date measles seems to be the most seriously incriminated virus in the etiopathogenesis of MS, mumps ranking second.


title: Serological evidence of viral orMycoplasma pneumoniae infection in acute maxillary sinusitis

text: Evidence for the involvement of viruses,Mycoplasma pneumoniae, andChlamydia spp. was studied by the complement fixation test in paired sera from 310 young adults (297 men and 13 women) with acute maxillary sinusitis. The diagnosis of acute sinusitis was confirmed by radiography and sinus puncture. Elevated antibody titres were found in 102 patients (33%). A four fold or greater titre rise was detected in 21.5%, and a high stable titre suggestive of recent viral infection was present in a further 11.5%. Adenovirus, influenza A and B viruses, andMycoplasma pneumoniae accounted for most of the elevated antibody titres. Elevated titres were found in 79 (32%) of the 245 patients with purulent maxillary sinusitis (pathogenic bacteria isolated in sinus secretion) and in 23 (35%) of the 65 patients with non-purulent sinusitis (no pathogenic bacteria isolated). About 90% of the fourfold or greater titre rises in bacteriologically negative cases were due to adeno- or influenza viruses. A fourfold rise in antibody titre was also found in 7 of 101 control patients (7%). The results of this study suggest that respiratory viruses andMycoplasma pneumoniae may be potential etiological agents in acute maxillary sinusitis, either alone or in combination with the common bacterial pathogens of sinusitis.


title: Observational study of newborn infant parasympathetic evaluation as a comfort system in awake patients admitted to a pediatric intensive care unit

text: To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. Comfort was evaluated using the COMFORT-behavior scale (CBS) before (T1), during (T2) and after (T3) each nebulization. In order to compare NIPE and CBS values during the whole T1 to T3 period, the variable Dif-CBS was defined as the difference between maximal and minimal CBS scores, and Dif-NIPE as the difference between 75th and 25th percentile NIPE values. Analyses were carried out, firstly for the total of nebulizations and secondly comparing two different nebulization systems: a jet nebulizer (JN) and a nebulizer integrated in high flow nasal cannulas (NHF). 84 nebulizations were recorded on 14 patients with a median [25th–75th percentile] age of 6 months (3.1–9.5). A Dif-CBS of 4 points (2–7), as well as changes in CBS scores between T1 and T2, defined the nebulization as a discomfort stimulus. The NIPE system, represented as the Dif-NIPE, showed a median variation of 9 points (7–10), and was poorly correlated to Dif-CBS [r(s) 0.162 (P = 0.142)]. Discomfort during nebulization, assessed by CBS was greater with the JN system compared to NHF: 17 (13–22) vs 13 (9–15) (P = 0.001). NIPE monitoring detected no significant differences between both nebulization systems (P = 0.706). NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. Further research is required before NIPE can be suggested as a comfort monitoring system for the awake infant.


International EcoHealth One Health Congress 2016


title: Visualization of sneeze ejecta: steps of fluid fragmentation leading to respiratory droplets

text: Coughs and sneezes feature turbulent, multiphase flows that may contain pathogen-bearing droplets of mucosalivary fluid. As such, they can contribute to the spread of numerous infectious diseases, including influenza and SARS. The range of contamination of the droplets is largely determined by their size. However, major uncertainties on the drop size distributions persist. Here, we report direct observation of the physical mechanisms of droplet formation at the exit of the mouth during sneezing. Specifically, we use high-speed imaging to directly examine the fluid fragmentation at the exit of the mouths of healthy subjects. We reveal for the first time that the breakup of the fluid into droplets continues to occur outside of the respiratory tract during violent exhalations. We show that such breakup involves a complex cascade of events from sheets, to bag bursts, to ligaments, which finally break into droplets. Finally, we reveal that the viscoelasticity of the mucosalivary fluid plays an important role in delaying fragmentation by causing the merger of the droplet precursors that form along stretched filaments; thereby affecting the final drop size distribution farther downstream. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00348-015-2078-4) contains supplementary material, which is available to authorized users.


docid: yujybbrm

title: Antiviral and Anticancer Activity of Cisplatin Derivatives of Tilorone

text: Cisplatin derivatives containing tilorone and a tilorone derivative were synthesized and characterized employing IR analysis, mass spectrometry, elemental analysis, and chain length. The polymeric cisplatin derivatives prevent growth of four transformed cell lines, L929, 143, Vero, and BS-C-1 and effectively inhibit four viruses including the DNA viruses; herpes simplex-1, vaccinia, and Varicella zoster, and the RNA virus, reovirus in the micrograms/mL range. The tilorone polymers display activity against both transformed cells and DNA and RNA viruses at biologically important concentrations.


Rechtliche Rahmenbedingungen für mobileHealth


title: A CA-based epidemic model for HIV/AIDS transmission with heterogeneity

text: The complex dynamics of HIV transmission and subsequent progression to AIDS make the mathematical analysis untraceable and problematic. In this paper, we develop an extended CA simulation model to study the dynamical behaviors of HIV/AIDS transmission. The model incorporates heterogeneity into agents’ behaviors. Agents have various attributes such as infectivity and susceptibility, varying degrees of influence on their neighbors and different mobilities. Additional, we divide the post-infection process of AIDS disease into several sub-stages in order to facilitate the study of the dynamics in different development stages of epidemics. These features make the dynamics more complicated. We find that the epidemic in our model can generally end up in one of the two states: extinction and persistence, which is consistent with other researchers’ work. Higher population density, higher mobility, higher number of infection source, and greater neighborhood are more likely to result in high levels of infections and in persistence. Finally, we show in four-class agent scenario, variation in susceptibility (or infectivity) and various fractions of four classes also complicates the dynamics, and some of the results are contradictory and needed for further research.


title: Targeting of proteins to the Golgi apparatus

text: The Golgi apparatus maintains a highly organized structure in spite of the intense membrane traffic which flows into and out of this organelle. Resident Golgi proteins must have localization signals to ensure that they are targeted to the correct Golgi compartment and not swept further along the secretory pathway. There are a number of distinct groups of Golgi membrane proteins, including glycosyltransferases, recyclingtrans-Golgi network proteins, peripheral membrane proteins, receptors and viral glycoproteins. Recent studies indicate that there are a number of different Golgi localization signals and mechanisms for retaining proteins to the Golgi apparatus. This review focuses on the current knowledge in this field.


title: Behavioral responses to the influenza A(H1N1) outbreak in Malaysia

text: In the setting of the new A(H1N1) outbreak, the study was conducted to assess: (1) fear of the A(H1N1) pandemic; (2) risk avoidance behavior; (3) health-protective behavior; and (4) psychosocial impact in the ethnically diverse population of Malaysia. A cross-sectional, computer-assisted telephone interview was conducted between July 11 and September 12, 2009. A total of 1,050 respondents were interviewed. Fear about the pandemic was high, with 73.2% of respondents reporting themselves as Slightly fearful/Fearful. High risk avoidance and health protective behavior were reported, with 78.0 and 99.0% reporting at least one avoidance and protective behavior respectively. Knowledge was a significant predictor for practice of healthprotective behavior across the three ethnic groups. Level of fear was significantly correlated with number of protective and avoidance behaviors. The study highlights the need for provision of accurate information that increases risk avoidance and health protective behaviors, while at the same time decreases fear or panic in the general public.


title: Cell surface effects of human immunodeficiency virus

text: Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes which could result in cell-cell fusion and single cell killing. The purpose of this model is to define the potential roles of individual viral envelope and cell surface molecules in cell killing processes and to identify alternative routes to the establishment of persistently-infected cells. Elucidation of HIV-induced cell surface effects may provide the basis for a rational approach to the design of antiviral agents which are selective for HIV-infected cells.


title: Time evolution of non-lethal infectious diseases: a semi-continuous approach

text: A model describing the dynamics related to the spreading of non-lethal infectious diseases in a fixed-size population is proposed. The model consists of a non-linear delay-differential equation describing the time evolution of the increment in the number of infectious individuals and depends upon a limited number of parameters. Predictions are in good qualitative agreement with data on influenza, which is taken to be a representative type of non-lethal infectious disease.


title: Large Context Problems and Their Applications to Education: Some Contemporary Examples

text: Some 35 years ago, Gerard K. O’Neill used the large context of space travel with his undergraduate physics students. A Canadian physics teacher, Art Stinner, independently arrived at a similar notion in a more limited but, therefore, more generally useful sense, which he referred to as the “large context problem” approach. At a slightly earlier time the large context problem type of approach had already been used in the study of medicine, pioneered by McMaster Medical School. And the Faculty of Education at the University of Calgary currently uses a large context problem method to deliver its entire curriculum. These approaches are four distinct ways of presenting large context problems to students. This paper will discuss these approaches historically, look at their grounds and their applications, weigh their successes and characterize their limitations. It will try to see what they take most deeply for granted as viable approaches to teaching science, both theoretical and applied. Finally, it will relate these approaches to the constructivist prejudices of our own time, suggesting their relation to earlier forms of philosophical idealism.


List of references


title: Tracing “Fearbola”: Psychological Predictors of Anxious Responding to the Threat of Ebola

text: Serious illnesses such as Ebola are often highly publicized in the mass media and can be associated with varying levels of anxiety and compensatory safety behavior (e.g., avoidance of air travel). The present study investigated psychological processes associated with Ebola-related anxiety and safety behaviors during the outbreak in late 2014. Between October 30 and December 3, 2014, which encompassed the peak of concerns and of the media’s attention to this particular outbreak, 107 university students completed a battery of measures assessing fear of Ebola, performance of safety behaviors, factual knowledge of the virus, and psychological variables hypothesized to predict Ebola-related fear. We found that while our sample was generally not very fearful of contracting Ebola, the fear of this disease was correlated with general distress, contamination cognitions, disgust sensitivity, body vigilance, and anxiety sensitivity-related physical concerns. Regression analyses further indicated that anxiety sensitivity related to physical concerns and the tendency to overestimate the severity of contamination were unique predictors of both Ebola fear and associated safety behaviors. Implications for how concerns over serious illness outbreaks can be conceptualized and clinically managed are discussed.


title: Comparison of six methods for detecting human rotavirus in stools

text: The following six methods for detecting rotavirus in human faecal samples were compared: electron microscopy, immune electron microscopy, immunofluorescence in cell culture, two enzyme immunoassays (Rotazyme, Enzygnost) and a latex agglutination test (Rotalex). Specimens were collected from 112 children with diarrhoea. The relative sensitivities of the different assays for human rotavirus were as follows: electron microscopy, 84%; immunofluorescence, 86%; Rotalex, 88%; Rotazyme, 89%; immune electron microscopy, 93%; Enzygnost, 98%. According to our findings Enzygnost is the most sensitive method, but Rotalex is more valuable for screening a small number of faecal samples. No false-positive results were observed in the two enzyme immunoassays or in Rotalex.


title: Isolation and study of the properties of an interferon-like inhibitor of viruses from normal human blood serum

text: A protein with a molecular weight of 17,400 daltons and an isoelectric point at pH 4.9 has been isolated from the blood serum of healthy donors by successive ion-exchange chromatography of QAE-Sephadex A-50, affinity chromatography on DNA-cellulose, and polyacrylamide gel electrophoresis, in the presence of sodium dodecyl sulfate. The protein isolated, like interferon, suppresses the development of the cytopathogenic action of the viruses of vesicular stomatitis and murine ecephalomyocarditis in cultures of human cells of the L-41 and M-19 lines. The amino acid composition of the protein isolated differs from those of various fractions of human interferons.


title: Privileged heterocycles: bioactivity and synthesis of 1,9-diazaspiro[5.5]undecane-containing compounds

text: This review discusses the biological activity and synthesis of 1,9-diazaspiro[5.5]undecanes, including those ring-fused with arenes and heteroarenes and/or containing a carbonyl group at position 2. These compounds could be used for the treatment of obesity, pain, as well as various immune system, cell signaling, cardiovascular, and psychotic disorders.


Viral genome cleavage with artificial ribonucleases: A new method to inactivate RNA-containing viruses


title: Estimating residue evolutionary conservation by introducing von Neumann entropy and a novel gap-treating approach

text: Evolutionary conservation derived from a multiple sequence alignment is a powerful indicator of the functional significance of a residue, and it can help to predict active sites, ligand-binding sites, and protein interaction interfaces. The results of the existing algorithms in identifying the residue’s conservation strongly depend on the sequence alignment, making the results highly variable. Here, by introducing the amino acid similarity matrix, we propose a novel gap-treating approach by combining the evolutionary information and von Neumann entropies to compute the residue conservation scores. It is indicated through a series of tested results that the new approach is quite encouraging and promising and may become a useful tool in complementing the existing methods.


title: Potential Inoculum Sources of Phaeomoniellachlamydospora in South African Grapevine Nurseries

text: Petri disease of grapevine is primarily caused by Phaeomoniella chlamydospora. This pathogen affects mostly young grapevines, but is also implicated in esca disease of older grapevines. Little is known about the disease cycle of this fungus. Infected propagation material was identified as a major means of dissemination of the pathogen. Recently, the pathogen was also detected from soil in South Africa and airborne conidia have been found in vineyards. The aim of this study was to use a molecular detection technique to test different samples collected from nurseries in South Africa at different nursery stages for the presence of P. chlamydospora. A one-tube nested-PCR technique was optimised for detecting P. chlamydospora in DNA extracted from soil, water, callusing medium and grapevine wood. The one-tube nested-PCR was sensitive enough to detect as little as 1 fg of P. chlamydospora genomic DNA from water and 10 fg from wood, callusing medium and soil. PCR analyses of the different nursery samples revealed the presence of several putative 360 bp P. chlamydospora specific bands. Subsequent sequence analyses and/or restriction enzyme digestions of all 360 bp PCR bands confirmed that all bands were P. chlamydospora specific, except for five bands obtained from callusing media and one from water. Phaeomoniella chlamydospora was positively detected in 25% of rootstock cane sections collected from mother blocks, 42% of rootstock cuttings and 16% of scion cuttings collected during grafting, 40% of water samples collected after pre-storage hydration, 67% of water samples collected during grafting, 8% of callusing medium samples and 17% of soil samples collected from mother blocks. These media can therefore be considered as possible inoculum sources of the pathogen during the nursery stages.


title: The long arm of climate change: societal teleconnections and the future of climate change impacts studies

text: “Societal teleconnections” – analogous to physical teleconnections such as El Niño – are human-created linkages that link activities, trends, and disruptions across large distances, such that locations spatially separated from the locus of an event can experience a variety of impacts from it nevertheless. In the climate change context, such societal teleconnections add a layer of risk that is currently neither fully appreciated in most impacts or vulnerability assessments nor in on-the-ground adaptation planning. Conceptually, societal teleconnections arise from the interactions among actors, and the institutions that guide their actions, affecting the movement of various substances through different structures and processes. Empirically, they arise out of societal interactions, including globalization, to create, amplify, and sometimes attenuate climate change vulnerabilities and impacts in regions far from those where a climatic extreme or change occurs. This paper introduces a simple but systematic way to conceptualize societal teleconnections and then highlights and explores eight unique but interrelated types of societal teleconnections with selected examples: (1) trade and economic exchange, (2) insurance and reinsurance, (3) energy systems, (4) food systems; (5) human health, (6) population migration, (7) communication, and (8) strategic alliances and military interactions. The paper encourages further research to better understand the causal chains behind socially teleconnected impacts, and to identify ways to routinely integrate their consideration in impacts/vulnerability assessment and adaptation planning to limit the risk of costly impacts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10584-015-1328-z) contains supplementary material, which is available to authorized users.


title: Lack of evidence of paratuberculosis in wild canids from Southwestern Europe

text: Wild carnivores are at the top of the trophic chain. They are predators and carrion consumers, and thus, prone to come in contact with disease agents contaminating the environment or infecting live or dead animals. We hypothesized that wild canids could be used as sentinels for the detection of regions with higher Mycobacterium avium paratuberculosis (MAP) prevalence in wild and domestic animals. To test this hypothesis, we set up an ELISA to test 262 wolf (Canis lupus) and fox (Vulpes vulpes) sera for MAP-specific antibodies and processed a subset of samples for culture (n = 61), MAP-specific PCR (15) and histopathology (14). In wolves, the optical density (OD) values in the ELISA were continuously distributed. Ten fox sera (4%) had OD readings of over twice the mean, suggesting contact with mycobacteria. However, all samples tested by PCR were negative for both IS900 and ISMAP02 sequences, and samples cultured for MAP yielded no growth. No visible paratuberculosis or tuberculosis-compatible lesions were recorded. On histopathological examination, no lesions compatible with mycobacterial diseases were observed. These results suggest that wild canids show little or no evidence of paratuberculosis and are unlikely to be useful sentinels for the detection of MAP in Southwestern Europe.


title: Clinical aspects of virus/immune myocarditis

text: Although a cause-and-effect relationship between viral infection and myocarditis remains inferential, two distinct clinical syndromes can be identified. During the early viral phase, the cardiac manifestations emerge while the symptoms of active viral infection are also present. During the chronic phase, symptoms of the viral infection may be remote or nonexistent, and identification of active myocarditis is contingent upon an aggressive diagnostic approach with endomyocardial biopsy and gallium 67 imaging. The exact incidence of myocarditis in patients with heart failure of unknown cause is unclear due to lack of standardization of histologic parameters. There are no other clinical clues to the presence of myocarditis in those patients presenting with cardiomyopathy or ventricular arrhythmia. For further clarification of the incidence and various presentations of myocarditis a large multi-center trial is necessary.


title: Prediction of mutations engineered by randomness in H5N1 neuraminidases from influenza A virus

text: In this proof-of-concept study, we attempt to determine whether the cause-mutation relationship defined by randomness is protein dependent by predicting mutations in H5N1 neuraminidases from influenza A virus, because we have recently conducted several concept-initiated studies on the prediction of mutations in hemagglutinins from influenza A virus. In our concept-initiated studies, we defined the randomness as a cause for mutation, upon which we built a cause-mutation relationship, which is then switched into the classification problem because the occurrence and non-occurrence of mutations can be classified as unity and zero. Thereafter, we used the logistic regression and neural network to solve this classification problem to predict the mutation positions in hemagglutinins, and then used the amino acid mutating probability to predict the would-be-mutated amino acids. As the previous results were promising, we extend this approach to other proteins, such as H5N1 neuraminidase in this study, and further address various issues raised during the development of this approach. The result of this study confirms that we can use this cause-mutation relationship to predict the mutations in H5N1 neuraminidases.


title: Gender influence on health and risk behavior in primary prevention: a systematic review

text: AIM: Prevention plays a crucial part in healthcare systems and is greatly influenced by the health and risk behavior of the population. The extent to which special tailoring to the addressed subjects would be helpful in improving the effectiveness of prevention measures is unknown. Therefore, the goal of this systematic review is to assess gender-specific differences in primary prevention actions. SUBJECT AND METHODS: A systematic review was conducted in 2015 by searching the PubMed (Medline) and Cochrane Library databases as well as adding additional studies by cross-referencing. The search focused on studies with an analysis of gender differences in health and risk behavior concerning primary prevention. Therefore, major exclusion criteria were single-gender studies, underage (<18 years) study collectives and secondary or tertiary prevention measures. RESULTS: In total, 23 studies from 13 different countries were included in the qualitative evaluation. The studies covered 11 different subtopics of primary prevention, but were too diverse in content and type to draw many fundamental conclusions. A meta-analysis was not possible. Generally a tendency for females to be more health-conscious and engaged in preventive behavior could be seen in most subgroups. CONCLUSION: The importance of gender-specific prevention measures for the healthcare system is being increasingly stressed, but only a few studies specifically analyzing the influence of gender on preventive behavior could be identified. To implement appropriate primary prevention measures tailored to gender-specific needs, more details and studies on gender differences are needed.


Necrotizing Enterocolitis of the Newborn: Pathogenetic Concepts in Perspective


title: In vitro plant tissue culture: means for production of biological active compounds

text: Plant tissue culture as an important tool for the continuous production of active compounds including secondary metabolites and engineered molecules. Novel methods (gene editing, abiotic stress) can improve the technique. Humans have a long history of reliance on plants for a supply of food, shelter and, most importantly, medicine. Current-day pharmaceuticals are typically based on plant-derived metabolites, with new products being discovered constantly. Nevertheless, the consistent and uniform supply of plant pharmaceuticals has often been compromised. One alternative for the production of important plant active compounds is in vitro plant tissue culture, as it assures independence from geographical conditions by eliminating the need to rely on wild plants. Plant transformation also allows the further use of plants for the production of engineered compounds, such as vaccines and multiple pharmaceuticals. This review summarizes the important bioactive compounds currently produced by plant tissue culture and the fundamental methods and plants employed for their production.


docid: lfeqwzjt

title: Health—exploring complexity: an interdisciplinary systems approach HEC2016: 28 August–2 September 2016, Munich, Germany


title: Neurovirulence of herpes simplex virus types 1 and 2 isolates in diseases of the central nervous system

text: Herpes simplex virus (HSV) isolates derived from the central nervous system of ten patients with HSV-1-induced encephalitis, one patient with multiple sclerosis, and 14 patients with HSV-2-induced meningitis were investigated for neurovirulence by assaying the LD(50) after nose and intracerebral (i.c.) inoculation of mice. HSV-1 encephalitis strains were significantly more virulent after nose inoculation (i.e. neuroinvasive) when compared with HSV-1 isolates from patients with oral lesions only, whereas HSV-2 meningitis strains were significantly more virulent after i.c. inoculation when compared with HSV-2 isolates from patients with genital lesions only. No correlation between high neurovirulence (defined as low LD(50) for both routes of infection) and replication in cell cultures of neuronal and non-neuronal cell lines was found, but the weakly neurovirulent HSV-1 strain isolated from a patient with multiple sclerosis gave low replication yields. After nose inoculation, a highly neuroinvasive HSV-1 laboratory reference strain replicated to high titers in nose tissue, the trigeminal ganglia and brainstem, while a strain with low neuroinvasiveness but high i.c. virulence replicated less well in the brainstem. Neuroinvasiveness of the virus strain might be one factor of relevance in the pathogenesis of HSV-1 encephalitis in man.


title: Unraveling the role of membrane microdomains during microbial infections

text: Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our understanding of the complex interactions between the host and specific bacterial, viral, and fungal pathogens. Lipid rafts are membrane microdomains that play important role in life cycle of microbes. Interaction of microbial pathogens with host membrane rafts influences not only their initial colonization but also their spread and the induction of inflammation. Therefore, intervention strategies aimed at modulating the assembly of membrane rafts and/or regulating raft-directed signaling pathways are attractive approaches for the. management of infectious diseases. The current review discusses the latest advances in terms of techniques used to study the role of membrane microdomains in various pathological conditions and provides updated information regarding the role of membrane rafts during bacterial, viral and fungal infections.


title: Identification of the site of translational frameshifting required for production of the transposase encoded by insertion sequence IS 1

text: Previous genetic analyses indicated that translational frameshifting in the −1 direction occurs within the run of six adenines in the sequence 5′-TTAAAAAACTC-3′ at nucleotide positions 305–315 in IS 1, where the two out-of-phase reading frames insA and B′-insB overlap, to produce transposase with a polypeptide segment Leu-Lys-Lys-Leu at residues 84–87. IS 1 mutants with a 1 by insertion, which encode mutant transposases with an amino acid substitution within the polypeptide segment at residues 84–87, did not efficiently mediate cointegration, except for an IS 1 mutant which encodes a mutant transposase with a Leu-Arg-Lys-Leu segment instead of Leu-LysLys-Leu. An IS 1 mutant with the DNA segment 5′-CTTAAAAACTC-3′ at positions 305–315 carrying the termination codon TAA in the B′-insB reading frame could still mediate cointegration, indicating that codon AAA for Lys corresponding to second, third and fourth positions in the run of adenines is the site of frameshifting. The β-galactosidase activity specified by several IS 1- lacZ fusion plasmids, in which B′-insB is in-frame with lacZ, showed that the region 292–377 is sufficient for frameshifting. The protein produced by frameshifting from the IS 1-lacZ plasmid in fact contained the polypeptide segment Leu - Lys - Lys - Leu encoded by the DNA segment 5′-TTAAAAAACTC-3′, indicating that −1 frameshifting does occur within the run of adenines.


title: Complete Nucleotide Sequence of Ryegrass Mottle Virus : A New Species of the Genus Sobemovirus

text: The genome of Ryegrass mottle virus (RGMoV) comprises 4210 nucleotides. The genomic RNA contains four open reading frames (ORFs). The largest ORF 2 encodes a polyprotein of 947 amino acids (103.6 kDa), which codes for a serine protease and an RNA-dependent RNA polymerase. The viral coat protein is encoded on ORF 4 present at the 3′-proximal region. Other ORFs 1 and 3 encode the predicted 14.6 kDa and 19.8 kDa proteins of unknown function. The consensus signal for frameshifting, heptanucleotide UUUAAAC and a stem-loop structure just downstream is in front of the AUG codon of ORF 3. Analysis of the in vitro translation products of RGMoV RNA suggests that the 68 kDa protein may represent a fusion protein of ORF 2-ORF 3 produced by frameshifting. The protease region of the polyprotein and coat protein have a low similarity with that of the sobemoviruses (approximately 25% amino acid identity), while the RNA-dependent RNA polymerase region has particularly strong similarity (54 to 60% of more than 350 amino acid residues). The sequence similarities of RGMoV to the sobemoviruses, together with the characteristic genome organization indicate that RGMoV is a new species of the genus Sobemovirus.


title: Acute respiratory infection due to Mycoplasma pneumoniae: current status of diagnostic methods

text: Because of the absence of well-standardized both in-house and FDA-approved commercially available diagnostic tests, the reliable diagnosis of respiratory infection due to Mycoplasma pneumoniae remains difficult. In addition, no formal external quality assessment schemes which would allow to conclude about the performance of M. pneumoniae diagnostic tests exist. In this review, the current state of knowledge of M. pneumoniae-associated respiratory infections in the context of epidemiological studies published during the past 5 years is discussed, with particular emphasis on the diagnostic strategies used and their impact on results. The role of M. pneumoniae as a cause of respiratory tract infections (RTIs) differs from study to study due to geographical and epidemiological differences, as well as to the application of different diagnostic techniques and criteria used. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-010-0975-2) contains supplementary material, which is available to authorized users.


title: Human melanoma invasion and metastasis enhancement by high expression of aminopeptidase N/CD13

text: Aminopeptidase N/CD13 is a Zn(2+)-dependent exoprotease present on the cell surface as a transmembrane protein. Our previous studies using aminopeptidase inhibitors and antibodies demonstrated that aminopeptidase N is involved in the degradation and invasion of the extracellular matrix (ECM) by metastatic tumor cells. In the present study we transfected human A375M melanoma cells with eukaryotic plasmid expression vectors that contained full length cDNA of aminopeptidase N/CD13 and examined their characteristics. The transfectants that expressed extremely high levels of aminopeptidase N/CD13 degraded type IV collagen and invaded ECM more actively than the parental and control vector-transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells had significantly augmented lung colonizing potential in nude mice. The results show that the aminopeptidase N/CD13 plays an active role in degradation and invasion of ECM and may be involved in the molecular mechanisms of blood-borne metastasis.


title: High-Mannose Specific Lectin and Its Recombinants from a Carrageenophyta Kappaphycus alvarezii Represent a Potent Anti-HIV Activity Through High-Affinity Binding to the Viral Envelope Glycoprotein gp120

text: We previously reported that a high-mannose binding lectin KAA-2 from the red alga Kappaphycus alvarezii, which is an economically important species and widely cultivated as a source of carrageenans, had a potent anti-influenza virus activity. In this study, the full-length sequences of two KAA isoforms, KAA-1 and KAA-2, were elucidated by a combination of peptide mapping and complementary DNA (cDNA) cloning. They consisted of four internal tandem-repeated domains, which are conserved in high-mannose specific lectins from lower organisms, including a cyanobacterium Oscillatoria agardhii and a red alga Eucheuma serra. Using an Escherichia coli expression system, an active recombinant form of KAA-1 (His-tagged rKAA-1) was successfully generated in the yield of 115 mg per liter of culture. In a detailed oligosaccharide binding analysis by a centrifugal ultrafiltration-HPLC method with 27 pyridylaminated oligosaccharides, His-tagged rKAA-1 and rKAA-1 specifically bound to high-mannose N-glycans with an exposed α1-3 mannose in the D2 arm as the native lectin did. Predicted from oligosaccharide binding specificity, a surface plasmon resonance analysis revealed that the recombinants exhibit strong interaction with gp120, a heavily glycosylated envelope glycoprotein of HIV with high association constants (1.48 − 1.61 × 10(9) M(−1)). Native KAAs and the recombinants inhibited the HIV-1 entry at IC(50)s of low nanomolar levels (7.3–12.9 nM). Thus, the recombinant proteins would be useful as antiviral reagents targeting the viral surface glycoproteins with high-mannose N-glycans, and the cultivated alga K. alvarezii could also be a good source of not only carrageenans but also this functional lectin(s).


Biological Resources and Migration


Surprise is a Neglected Aspect of Emerging Infectious Disease


Grundrechtliche Fragen der Xenotransplantation


docid: fvvgbwwq

title: International health in a globalized development perspective

text: Eleven issues highlight the relation between globalization and health: 1. Globalization endangers health. Risks are spreading. AIDS and SARS are examples. 2. Global alliances are emerging to protect health, especially fighting AIDS, malaria and tuberculosis. 3. In many millennium declarations, health was declared a worldwide development goal. 4. The international development cooperation for health is ailing everywhere despite three good reasons to make health a priority. 5. Good health supports good politics and national security. 6. The lack of security in health is an essential trap of poverty and increases population growth. 7. Health has essential macroeconomic benefits. Leading economists have made this clear. 8. Thus, health and education are true keys to social and economic development. Brains and bodies are the most essential factors of production. 9. “Empowerment in security creates opportunities”. This new motto underlines the strategic importance of health literacy and social health insurance. 10. International or global health is a leitmotiv of this decade of development. 11. Globalization requires powerful ethics to gain a human face. Professional ethics and a rebellious civil society ought to be allies. Current globalization is both a threat and a positive challenge, indeed.


title: Biobanking and public health: is a human rights approach the tie that binds?

text: Ethical principles guiding public health and genomic medicine are often at odds: whereas public health practice adopts collectivist principles that emphasize population-based benefits, recent advances in genomic and personalized medicine are grounded in an individualist ethic that privileges informed consent, and the balancing of individual risk and benefit. Indeed, the attraction of personalized medicine is the promise it holds out to help individuals get the “right medicine for the right problem at the right time.” Research biobanks are an effective tool in the genomic medicine toolbox. Biobanking in public health presents a unique case study to unpack some of these issues in more detail. For example, there is a long history of using banked tissue obtained under clinical diagnostic conditions for later public health uses. But despite the collectivist approach of public health, the principles applied to the ethical challenges of biobanking (e.g. informed consent, autonomy, privacy) remain individualist. We demonstrate the value of using human rights as a public health ethics framework to address this tension in biobanking by applying it to two illustrative cases.


title: GeoWeb and crisis management: issues and perspectives of volunteered geographic information

text: Mapping, and more generally geopositioning, has become ubiquitous on the Internet. This democratization of geomatics through the GeoWeb results in the emergence of a new form of mapping based on Web 2.0 technologies. Described as Web-mapping 2.0, it is especially characterized by high interactivity and geolocation-based contents generated by users. A series of recent events (hurricanes, earthquakes, pandemics) have urged the development of numerous mapping Web applications intended to provide information to the public, and encourage their contribution to support crisis management. This new way to produce and spread geographic information in times of crisis brings up many questions and new potentials with regard to urgency services, Non Governmental Organisations (NGO), as well as individuals. This paper aims at putting into perspective the development of GeoWeb, both in terms of technologies and applications, against crisis management processes.


docid: bqrkctzb

title: Exhaustive exercise reduces TNF-α and IFN-α production in response to R-848 via toll-like receptor 7 in mice

text: Stressful exercise results in temporary immune depression. However, the impact of exercise on the immune responses via toll-like receptor (TLR) 7, which recognizes the common viral genomic feature, single-stranded RNA, remains unclear. To clarify the effect of stressful exercise on immune function in response to viral infection, we measured the changes in the plasma concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-α, which are induced downstream from the TLR–ligand interaction, in exhaustive-exercised mice immediately after treatment with the imidazoquinoline R-848, which can bind to and activate TLR7. Both exhaustive-exercised (EX) and non-exercised (N-EX) male C3H/HeN mice were injected with R-848 (5 mg kg(−1)), and blood samples were collected. In addition, RAW264 cells, which are mouse macrophage cells, were cultured 30 min after epinephrine (10 μM) or norepinephrine (10 μM) treatments, and were then stimulated with R-848 (10 μg ml(−1)). In addition, the effect of propranolol (10 mg kg(−1)) as blockade of β-adrenergic receptors on R-848-induced TNF-α and IFN-α production in the exercised mice was examined. Both the TNF-α and IFN-α concentrations in the plasma of EX were significantly lower than those in the plasma of N-EX after R-848 injection (P < 0.05 and P < 0.01, respectively), although the R-848 treatment increased the plasma TNF-α and IFN-α concentrations in both groups (P < 0.01, respectively). The R-848-induced TNF-α production in RAW264 cells was significantly inhibited by epinephrine and norepinephrine pre-treatment, although IFN-α was not detected. The propranolol treatment completely inhibited exercise-induced TNF-α and IFN-α suppression in response to R-848 in the mice. These data suggest that EX induces a reduction in TNF-α and IFN-α production in response to R-848, and that these phenomena might be regulated by an exercise-induced elevation of the systemic catecholamines.


title: Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance

text: Methicillin-resistant Staphylococcus aureus (MRSA) is able to persist not only in hospitals (with a high level of antimicrobial agent use) but also in the community (with a low level of antimicrobial agent use). The former is called hospital-acquired MRSA (HA-MRSA) and the latter community-acquired MRSA (CA-MRSA). It is believed MRSA clones are generated from S. aureus through insertion of the staphylococcal cassette chromosome mec (SCCmec), and outbreaks occur as they spread. Several worldwide and regional clones have been identified, and their epidemiological, clinical, and genetic characteristics have been described. CA-MRSA is likely able to survive in the community because of suitable SCCmec types (type IV or V), a clone-specific colonization/infection nature, toxin profiles (including Pantone-Valentine leucocidin, PVL), and narrow drug resistance patterns. CA-MRSA infections are generally seen in healthy children or young athletes, with unexpected cases of diseases, and also in elderly inpatients, occasionally surprising clinicians used to HA-MRSA infections. CA-MRSA spreads within families and close-contact groups or even through public transport, demonstrating transmission cores. Re-infection (including multifocal infection) frequently occurs, if the cores are not sought out and properly eradicated. Recently, attention has been given to CA-MRSA (USA300), which originated in the US, and is growing as HA-MRSA and also as a worldwide clone. CA-MRSA infection in influenza season has increasingly been noted as well. MRSA is also found in farm and companion animals, and has occasionally transferred to humans. As such, the epidemiological, clinical, and genetic behavior of CA-MRSA, a growing threat, is focused on in this study.


title: Import of West Nile Virus Infection in the Czech Republic

text: We report West Nile virus infection of the central nervous system in a 69-year-old man, residing in North Moravia (Czech Republic), who visited the USA from 6 July to 31 August 2002. He developed fever with fatigue at the end of his US stay, and was hospitalized in Ostrava after his return on 3 September with fever (up to 39.5 °C), fatigue, anorexia, moderate laryngotracheitis, dizziness, insomnia, blurred speech, and a marked bradypsychism. EEG demonstrated a slow bifrontal theta–delta activity, and CT of the brain a slight hydrocephalus. A significant increase of antibodies neutralizing West Nile virus was detected between the first (1:16) and second (1:256) blood serum sample. The patient recovered gradually and was released from hospital on 16 September. This is the first recorded human case of West Nile fever (WNF) imported to the Czech Republic. Nine similar cases of WNF import from the USA have already been reported in other European countries – France, Denmark, the Netherlands, and Germany.


title: Experimental Biology for the Identification of Causal Pathways in Atherosclerosis

text: More than 60 genomic loci have been implicated by genome-wide association studies (GWAS) and exome-wide association studies as conferring an increased risk of myocardial infarction and coronary artery disease (CAD). However, the causal gene and variant is often unclear. Using the functional analysis of genetic variants in experimental animal models, we anticipate understanding which candidate gene at a specific locus is associated with atherosclerosis and revealing the underlying molecular and cellular mechanisms, ultimately leading to the identification of causal pathways in atherosclerosis and may provide novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease.


title: The need for European professional standards and the challenges facing clinical microbiology

text: Microorganisms spread across national boundaries and the professional activities of clinical (medical) microbiologists are critical in minimising their impact. Clinical microbiologists participate in many activities, e.g. diagnosis, antibiotic therapy, and there is a need for a set of professional standards for Europe with a common curriculum, to build upon the current strengths of the specialty and to facilitate the free movement of specialists within the European Union. Such standards will also better highlight the important contribution of clinical microbiologists to healthcare. There is a move to larger centralised microbiology laboratories often located off-site from an acute hospital, driven by the concentration of resources, amalgamation of services, outsourcing of diagnostics, automation, an explosion in the range of staff competencies and accreditation. Large off-site centralised microbiology laboratories are often distant to the patient and may not facilitate the early detection of microbial spread. Ultimately, the needs of patients and the public are paramount in deciding on the future direction of clinical microbiology. Potential conflicts between integration on an acute hospital site and centralisation can be resolved by a common set of professional standards and a team-based approach that puts patients first.


Is the global economy on the brink of recession?


title: DNA sequences required for translational frameshifting in production of the transposase encoded by IS 1

text: The transposase encoded by insertion sequence IS 1 is produced from two out-of-phase reading frames (insA and B′-insB) by translational frameshifting, which occurs within a run of six adenines in the −1 direction. To determine the sequence essential for frameshifting, substitution mutations were introduced within the region containing the run of adenines and were examined for their effects on frameshifting. Substitutions at each of three (2nd, 3rd and 4th) adenine residues in the run, which are recognized by tRNA(Lys) reading insA, caused serious defects in frameshifting, showing that the three adenine residues are essential for frameshifting. The effects of substitution mutations introduced in the region flanking the run of adenines and in the secondary structures located downstream were, however, small, indicating that such a region and structures are not essential for frameshifting. Deletion of a region containing the termination codon of insA caused a decrease in β-galactosidase activity specified by the lacZ fusion plasmid in frame with B′-insB. Exchange of the wild-type termination codon of insA for a different one or introduction of an additional termination codon in the region upstream of the native termination codon caused an increase in β-galactosidase activity, indicating that the termination codon in insA affects the efficiency of frameshifting.


Treatment of chronic hepatitis C patients not responding to combination therapy with ribavirin and interferon α — hype or hope?