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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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
“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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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). |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
Innovation diffusion theory proposed that adopters—whether individuals or organizations—sometimes reinvent an innovation as they gain experience using it. Reinvention can enhance (or impede) the likelihood of an IS innovation’s acceptance and further diffusion. This paper reports on a case study of BioSense, an interorganizational system that was designed as an early detection tool for bio-terror attacks and subsequently modified to better serve this need as well as to operate as a public health system for pinpointing geographic clusters of dangerous/acute disease outbreaks. By examining the interplay among the political and organizational dynamics and technical properties of the BioSense system, we shed light on processes affecting reinvention in an interorganizational context. We discuss our findings in light of theories of the diffusion and reinvention of innovations. We use Rogers’ (1995) list of factors supporting reinvention to structure the discussion of the fidelity and uniformity of the innovation within the processes it supports in adopting health services organizations. |
This article categorizes four kinds of adverse effects to human health caused by ecosystem change: direct, mediated, modulated, and systems failure. The effects are categorized on their scale, complexity, and lag-time. Some but not all of these can be classified as resulting from reduced ecosystem services. The articles also explores the impacts that different socioeconomic–ecologic scenarios are likely to have on human health and how changes to human health may, in turn, influence the unfolding of four different plausible future scenarios. We provide examples to show that our categorization is a useful taxonomy for understanding the complex relationships between ecosystems and human well-being and for predicting how future ecosystem changes may affect human health. |
This article analyzes the current situation in the field of construction and production of pandemic influenza vaccines. The main task of protecting the population against influenza pandemics requires state-of-the-art approaches to the construction of influenza vaccines to be based on reassortment and genetic engineering techniques, including the analysis of primary structures of influenza viral genes, synthesis and cloning of the main viral genes, reverse genetics techniques, and banks of plasmids bearing basic viral genes. Reassortant technologies are now giving way to new approaches for objective reasons. The state-of-the-art technologies provide safety not only at the laboratories where vaccine viruses are constructed but also make the production process wholly safe. We are using the following approaches to the development of industrial production: use of nanoparticles and nanoemulsions as functional adjuvants, construction of totally-safe strains for live attenuated influenza vaccines with deletions of molecular determinants of pathogenicity, application of protein and chemical chaperones to provide self-assembly of haemagglutinin molecules of the H1N1v-2009 virus, and impregnation of whole-virion preparations with nanoparticles to enhance antigenicity. |
To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found that, compared to seronegative controls, mice that were seropositive at least to Mouse Hepatitis Virus (MHV) and Mycoplasma pulmonis: (i) exhibited a higher interindividual variability in all the parameters quantifying metastatic progression; (ii) had elevated serum levels of proinflammatory cytokines both before and at the end of the experiment; (iii) were more susceptible to hepatic metastasis. Interestingly, final levels of tumor necrosis factor (TNF)-α and interleukin (IL)-18 correlated with the extent of hepatic colonization by the melanoma cells. To confirm the metastasis-enhancing effect of MHV and M. pulmonis we measured the ability of B16M cells to metastasize in pathogen-free animals housed for increasing time-intervals in the vicinity of MHV(+) animals. Notably, susceptibility to metastasis was lower in animals seronegative to MHV than in MHV(+) mice, whereas the latter were less susceptible to metastasis than MHV(+) M. pulmonis(+) mice. Seropositive animals had increased levels of TNF-α and IL-18 suggesting that MHV and M. pulmonis enhance the metastatic ability of melanoma cells by inducing the release of proinflammatory cytokines. While our results highlight the importance of using pathogen-free animals in metastasis studies, they emphasize the need for a comprehensive health monitoring of the mice used in such studies, particularly in case of using facilities lacking appropriate containment measures. |
We address the question of understanding the effect of the underlying network topology on the spread of a virus and the dissemination of information when users are mobile performing independent random walks on a graph. To this end, we propose a simple model of infection that enables to study the coincidence time of two random walkers on an arbitrary graph. By studying the coincidence time of a susceptible and an infected individual both moving in the graph we obtain estimates of the infection probability. The main result of this paper is to pinpoint the impact of the network topology on the infection probability. More precisely, we prove that for homogeneous graphs including regular graphs and the classical Erdős–Rényi model, the coincidence time is inversely proportional to the number of nodes in the graph. We then study the model on power-law graphs, that exhibit heterogeneous connectivity patterns, and show the existence of a phase transition for the coincidence time depending on the parameter of the power-law of the degree distribution. We finally undertake a preliminary analysis for the case with k random walkers and provide upper bounds on the convergence time for both the complete graph and regular graphs. |
It has been argued that moral problems in relation to Information Technology (IT) require new theories of ethics. In recent years, an interesting new theory to address such concerns has been proposed, namely the theory of Information Ethics (IE). Despite the promise of IE, the theory has not enjoyed public discussion. The aim of this paper is to initiate such discussion by critically evaluating the theory of IE. |
The pathogenesis of diarrhea caused by rotavirus infection was studied in miniature swine piglets. The animals were inoculated orally with 2×10(7) plaque-forming units of porcine rotavirus (OSU strain). During the height of diarrhea, intestinal function was investigated byin vivo perfusion of a 30-cm segment of proximal jejunum and a 30-cm segment of distal ileum. Absorption of Na(+) and water decreased and 3-O-methylglucose transport was markedly reduced,P<0.01 compared to control animals. Mucosal lactase and sucrase levels were depressed in both the jejunum and ileum,P<0.001. Na(+), K(+)-ATPase activity was significantly depressed only in the ileum,P<0.001. These changes were associated with a marked reduction in villous height, suggesting that the diarrhea could be an osmotic diarrhea due to nutrient (carbohydrate) malabsorption. Fresh stool samples were obtained and analyzed immediately for NA(+),K(+), osmolarity, glucose, and lactose; the osmotic gap was also determined. Stool osmolarity continually increased from 248±20 mosm/liter prior to inoculation to 348±20 mosm/liter at 75±1 hr postinoculation (P<0.005); the majority of the fecal osmotic gap could be accounted for by the amount of lactose present in the stools. Stool sodium increased from 34±6 mM prior to inoculation to a maximum of 65±4 mM at 53±1 hr postinoculation,P<0.001. There was no significant change in potassium concentration. The present investigation suggests that rotavirus-induced diarrhea is due to virus destruction of enterocytes lining the intestinal villi, thus reducing the mucosal surface area and important digestive enzymes. This destruction leads to an osmotic diarrhea due to nutrient (primarily carbohydrate) malabsorption. A possible contributing role of unopposed secretion from the crypt cannot be excluded from this study. |
Asarum caudigerum (Aristolochiaceae) is a paleoherb species that is important for research in origin and evolution of angiosperm flowers due to its basal position in the angiosperm phylogeny. In this study, a subtracted floral cDNA library from floral buds of A. caudigerum was constructed and cDNA arrays by suppression subtractive hybridization were generated. cDNAs of floral buds at different stages before flower opening and of leaves at the seedling stage were used. The macroarray analyses of expression profiles of isolated floral genes showed that 157 genes out of the 612 unique ESTs tested revealed higher transcript abundance in the floral buds and uppermost leaves. Among them, 78 genes were determined to be differentially expressed in the perianth, 62 in the stamens, and 100 genes in the carpels. Quantitative real-time PCR of selected genes validated the macroarray results. Remarkably, APETALA3 (AP3) B-class genes isolated from A. caudigerum were upregulated in the perianth, stamens and carpels, implying that the expression domain of B-class genes in this basal angiosperm was broader than those in their eudicot counterparts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00425-009-1048-6) contains supplementary material, which is available to authorized users. |
Network immunization strategies have emerged as possible solutions to the challenges of virus propagation. In this paper, an existing interactive model is introduced and then improved in order to better characterize the way a virus spreads in email networks with different topologies. The model is used to demonstrate the effects of a number of key factors, notably nodes’ degree and betweenness. Experiments are then performed to examine how the structure of a network and human dynamics affects virus propagation. The experimental results have revealed that a virus spreads in two distinct phases and shown that the most efficient immunization strategy is the node-betweenness strategy. Moreover, those results have also explained why old virus can survive in networks nowadays from the aspects of human dynamics. |
Influenza pandemics have occurred intermittently throughout the 20th century and killed millions of people worldwide. It is expected that influenza pandemics will continue to occur in the near future. Huge number of deaths and cases is the most troublesome aspect of the influenza pandemics, but the other important trouble is the economic impact of the influenza pandemics to the countries. In this study, we try to detect the cost of a possible influenza pandemic under different scenarios and attack rates. We include the vaccination and antiviral treatment cost for direct cost and we add the work absenteeism cost to the calculations for indirect cost of influenza pandemics. As a case study, we calculate the economic impact of pandemic influenza for Turkey under three different scenarios and three different attack rates. Our optimistic estimation shows that the economic impact of pandemic influenza will be between 1.364 billion dollars and 2.687 billions dollars to Turkish economy depending on the vaccination strategies. |
Topic Detection and Tracking (TDT) is a research initiative that aims at techniques to organize news documents in terms of news events. We propose a method that incorporates simple semantics into TDT by splitting the term space into groups of terms that have the meaning of the same type. Such a group can be associated with an external ontology. This ontology is used to determine the similarity of two terms in the given group. We extract proper names, locations, temporal expressions and normal terms into distinct sub-vectors of the document representation. Measuring the similarity of two documents is conducted by comparing a pair of their corresponding sub-vectors at a time. We use a simple perceptron to optimize the relative emphasis of each semantic class in the tracking and detection decisions. The results suggest that the spatial and the temporal similarity measures need to be improved. Especially the vagueness of spatial and temporal terms needs to be addressed. |
• BACKGROUND: Different viruses have been reported to be involved in retinal diseases in animalsystems. In humans, herpes simplex virus and cytomegalovirus have been found to cause retinal disease. Most of the studied viruses are neurotropic. In this study, the in vitro susceptibility of human retinal pigment epithelial cells (RPEC) to representative members of different groups of human pathogenic viruses was investigated. • METHODS: Early cultures of RPE C — after two or three passages — were infected with the following viruses: herpes simplex virus (HSV) type 1, human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus types 1 and 7, measles virus, parainfluenza virus and coxsackie virus B3. • RESULTS: Cultures of RPE C could be infected with neurotropic viruses like HSV or measles virus as well as with typical respiratory viruses like parainfluenza or adenoviruses. Coxsackievirus, an enterovirus, replicated as well as human CMV whereas EBV and HHV-6, two lymphotropic viruses, failed to infect RPE. • CONCLUSION: These findings suggest that a variety of viruses, including those causing rather common illnesses, might be capable of inducing retinal lesions under certain circumstances due to haematogenous spread during the course of viraemia. |
Infectious diseases and cancers are some of the commonest causes of deaths throughout the world. The previous two decades have witnessed a combined endeavor across various biological sciences to address this issue in novel ways. The advent of recombinant DNA technologies has provided the tools for producing recombinant proteins that can be used as therapeutic agents. A number of expression systems have been developed for the production of pharmaceutical products. Recently, advances have been made using plants as bioreactors to produce therapeutic proteins directed against infectious diseases and cancers. This review highlights the recent progress in therapeutic protein expression in plants (stable and transient), the factors affecting heterologous protein expression, vector systems and recent developments in existing technologies and steps towards the industrial production of plant-made vaccines, antibodies, and biopharmaceuticals. |
In the 21st century, public health is not only challenged by newly emerging and re-emerging infectious diseases but also by demographic developments that are taking place in many countries. Importantly, infections in the elderly are more frequent, more severe and have distinct features with respect to clinical presentation and treatment. This is due to a decline in the functions of the immune system referred to as immunosenescence. The most important age-related changes affect the T cell system. Although this derogates the protective effect of some vaccines, vaccinations are still considered the most cost-effective medical procedure for preventing morbidity and mortality caused by infectious diseases. The present article aims at outlining the impact of infectious diseases on the elderly and summarizing the progress made in the field of vaccinations of the elderly and how age-related changes within the immune system contribute to the decreased efficacy of vaccines. |
Two previously identified forms of macrophage were investigated in primary cultures of cerebral cortical cells. Dynamic features were revealed through time-lapse video recording and aspects of macrophage function were assessed. The two cell forms were shown to be different pre-mitotic stages of a single cell type. The cell cycle for these cells involved an initial large, flat, quiescent cell which retracted to yield a slightly rounded form with numerous processes. This latter form lost processes and developed profuse filopodia as it became very rounded just prior to division; both resulting daughter cells then regained the initial large flat appearance. These cells possessed several properties of macrophages, including phagocytosis, nucleoside diphosphatase enzyme, and CR3 receptors. These properties were transient, expressed just before and after mitosis, but subsequently down-regulated in the flat daughter cells. Because of this feature, it was difficult to determine the exact size of this cell population; however, the observed rate of proliferation suggests it may be substantial. It is suggested that these cells correspond to non-microglial macrophages of brain tissue and, because of their significant down-regulation, they may be difficult to detect. This may be important in studies of brain accessory immune cells in tissue culture. |
The 2014–2015 outbreak of the Ebola virus disease (EVD) in West Africa has been considered a major global health emergency by the WHO. Implications for health care providers including oral and maxillo-facial surgeons have been published by the WHO, the Centers for Disease Control and Prevention (USA), and other medical societies and public health organizations. While the risk of infection with the Ebola virus seems to be rather small in Europe, maxillo-facial and plastic surgeons often travel to Africa to treat patients with facial burns, cleft-lip and palate, and noma. The likelihood of an encounter with patients infected by Ebola virus in subsaharan and West Africa, therefore, has increased during the last 2 years. The purpose of this short overview was to summarize the virology of the Ebola virus, transmission, epidemiology, clinical features, oral manifestations, treatment, and possible implications for maxillo-facial surgeons of EDV. |
Pandemic influenza is considered catastrophic to global health, with severe economic and social effects. Consequently, a strategy for the rapid deployment of essential medical supplies used for the prevention of influenza transmission and to alleviate public panic caused by the expected shortage of such supplies needs to be developed. Therefore, we employ integrated information concepts to develop a simulated influenza medical material supply system to facilitate a rapid response to such a crisis. Various scenarios are analyzed to estimate the appropriate inventory policy needed under different pandemic influenza outbreaks, and to establish a mechanism to evaluate the necessary stockpiles of medications and other requirements in the different phases of the pandemic. This study constructed a web-based decision support system framework prototype that displayed transparent data related to medical stockpiles in each district and integrated expert opinion about the best distribution of these supplies in the influenza pandemic scenarios. A data collection system was also designed to gather information through a daily VPN transmitted into one central repository for reporting and distribution purposes. This study provides timely and transparent medical supplies distribution information that can help decision makers to make the appropriate decisions under different pandemic influenza outbreaks, and also attempts to establish a mechanism of evaluating the stockpiles and requirements in the different phases of the pandemic. |
In May and September, 2002, 14 private residential drinking water wells, one dewatering well at a lignite mine, eight surface water sites, and lignite from an active coal mine were sampled in five Parishes of northwestern Louisiana, USA. Using a geographic information system (GIS), wells were selected that were likely to draw water that had been in contact with lignite; control wells were located in areas devoid of lignite deposits. Well water samples were analyzed for pH, conductivity, organic compounds, and nutrient and anion concentrations. All samples were further tested for presence of fungi (cultures maintained for up to 28 days and colonies counted and identified microscopically) and for metal and trace element concentration by inductively-coupled plasma mass spectrometry and atomic emission spectrometry. Surface water samples were tested for dissolved oxygen and presence of pathogenic leptospiral bacteria. The Spearman correlation method was used to assess the association between the endpoints for these field/laboratory analyses and incidence of cancer of the renal pelvis (RPC) based on data obtained from the Louisiana Tumor Registry for the five Parishes included in the study. Significant associations were revealed between the cancer rate and the presence in drinking water of organic compounds, the fungi Zygomycetes, the nutrients PO(4) and NH(3), and 13 chemical elements. Presence of human pathogenic leptospires was detected in four out of eight (50%) of the surface water sites sampled. The present study of a stable rural population examined possible linkages between aquifers containing chemically reactive lignite deposits, hydrologic conditions favorable to the␣leaching and transport of toxic organic compounds from the lignite into the groundwater, possible microbial contamination, and RPC risk. |
Pneumoviruses have been identified as causative agents in several respiratory disease outbreaks in habituated wild great apes. Based on phylogenetic evidence, transmission from humans is likely. However, the pathogens have never been detected in the local human population prior to or at the same time as an outbreak. Here, we report the first simultaneous detection of a human respiratory syncytial virus (HRSV) infection in western lowland gorillas (Gorilla gorilla gorilla) and in the local human population at a field program in the Central African Republic. A total of 15 gorilla and 15 human fecal samples and 80 human throat swabs were tested for HRSV, human metapneumovirus, and other respiratory viruses. We were able to obtain identical sequences for HRSV A from four gorillas and four humans. In contrast, we did not detect HRSV or any other classic human respiratory virus in gorilla fecal samples in two other outbreaks in the same field program. Enterovirus sequences were detected but the implication of these viruses in the etiology of these outbreaks remains speculative. Our findings of HRSV in wild but human-habituated gorillas underline, once again, the risk of interspecies transmission from humans to endangered great apes. |
Bacteriophage T7 infection has been studied in Escherichia coli strains showing both increased and decreased ribosome fidelity and in the presence of streptomycin, which stimulates translational misreading, in an effort to determine effects on the apparent programmed translational frameshift that occurs during synthesis of the gene 10 capsid protein. Quantitation of the protein bands from SDS-PAGE failed to detect any significant effects on the amounts of the shifted 10B protein relative to the in-frame 10A protein under all fidelity conditions tested. However, any changes in fidelity conditions led to inhibition of phage morphogenesis in single-step growth experiments, which could not be accounted for by reduced amounts of phage protein synthesis, nor, at least in the case of decreased accuracy, by reduced amounts of phage DNA synthesis. Reduction in phage DNA synthesis did appear to account for a substantial proportion of the reduction in phage yield seen under conditions of increased accuracy. Similar effects of varying ribosomal fidelity on growth were also seen with phage T3, and to a lesser extent with phage T4. The absence of change in the high-frequency T7 gene 10 frameshift differs from earlier reports that ribosomal fidelity affects low-frequency frameshift errors. |
Microfluidic particle counters are important tools in biomedical diagnostic applications such as flow cytometry analysis. Major methods of counting particles in microfluidic devices are reviewed in this paper. The microfluidic resistive pulse sensor advances in sensitivity over the traditional Coulter counter by improving signal amplification and noise reduction techniques. Nanopore-based methods are used for single DNA molecule analysis and the capacitance counter is useful in liquids of low electrical conductivity and in sensing the changes of cell contents. Light-scattering and light-blocking counters are better for detecting larger particles or concentrated particles. Methods of using fluorescence detection have the capability for differentiating particles of similar sizes but different types that are labeled with different fluorescent dyes. The micro particle image velocimetry method has also been used for detecting and analyzing particles in a flow field. The general limitation of microfluidic particle counters is the low throughput which needs to be improved in the future. The integration of two or more existing microfluidic particle counting techniques is required for many practical on-chip applications. |
The +1 frameshift mutation, M5631, which is located in the gene (oxi1) for cytochrome c oxidase II (COXII) of the yeast mitochondrial genome, is suppressed spontaneously to a remarkably high extent (20%–30%). The full-length wild-type COXII produced as a result of suppression allows the mutant strain to grow with a “leaky” phenotype on non-fermentable medium. In order to elucidate the factors and interactions involved in this translational suppression, the strain with the frameshift mutation was mutated by MnCl(2) treatment and a large number of mutants showing restriction of the suppression were isolated. Of 20 mutants exhibiting a strong, restricted, respiration-deficient (RD) phenotype, 6 were identified as having mutations in the mitochondrial genome. Furthermore, genetic analyses mapped one mutation to the vicinity of the gene for tRNA(Pro) and two others to a region of the tRNA cluster where two-thirds of all mitochondrial tRNA genes are encoded. The degree of restriction of the spontaneous frameshift suppression was characterized at the translational level by in vivo (35)S-labeling of the mitochondrial translational products and immunoblotting. These results showed that in some of these mutant strains the frameshift suppression product is synthesized to the same extent as in the leaky parent strain. It is suggested that more than one +1 frame-shifted product is made as a result of suppression in these strains: one is as functional as the wild-type COXII, the other(s) is (are) non-functional and prevent leaky growth on non-fermentable medium. A possible mechanism for this heterogenous frameshift suppression is discussed. |
This is the continuation of our studies on the prediction of mutation engineered by randomness in proteins from influenza A virus. In our previous studies, we have demonstrated that randomness plays a role in engineering mutations because the measures of randomness in protein are different before and after mutations. Thus we built a cause-mutation relationship to count the mutation engineered by randomness, and conducted several concept-initiated studies to predict the mutations in proteins from influenza A virus, which demonstrated the possibility of prediction of mutations along this line of thought. On the other hand, these concept-initiated studies indicate the directions forwards the enhancement of predictability, of which we need to use the neural network instead of logistic regression that was used in those concept-initiated studies to enhance the predictability. In this proof-of-concept study, we attempt to apply the neural network to modeling the cause-mutation relationship to predict the possible mutation positions, and then we use the amino acid mutating probability to predict the would-be-mutated amino acids at predicted positions. The results confirm the possibility of use of internal cause-mutation relationship with neural network model to predict the mutation positions and use of amino acid mutating probability to predict the would-be-mutated amino acids. |
AIM: In this original article, we seek to analyse the environment in which immunisation policies are adopted and, more specifically, the way the public perception of vaccines influences decision-making, by looking more closely at the case of Switzerland. SUBJECTS AND METHODS: Historical and present-day examples of attitudes towards immunisation and specific vaccines, both on the part of the public and of health-care workers, are reviewed. RESULTS: Decision-making with regard to vaccine policy implementation has been and is still most often driven by fear: fear of disease (when perceived as rampant and/or dangerous), but also fear of vaccine-associated adverse events (when the disease is less or no longer “visible”). However, methodology for introducing evidence-based immunisation policies exists and can be used by public health authorities, while vaccination information systems (such as the Swiss InfoVac) have proven their usefulness in providing trustworthy, peer-based knowledge to health-care workers. CONCLUSION: Only information based on clear, evidence-based data gathered and analysed according to solid methodological criteria coupled with adequate information of health-care workers (and thus patients) can ensure in future the implementation of scientifically coherent, publicly acceptable, and equitable immunisation policies. |
An inexpensive, disposable, integrated, polymer-based cassette for loop-mediated isothermal amplification (LAMP) of target nucleic acids was designed, fabricated, and tested. The LAMP chamber was equipped with single-use, thermally actuated valves made with a composite consisting of a mixture of PDMS and expandable microspheres. The effect of the composite composition on its expansion was investigated, and the valve’s performance was evaluated. In its closed state, the valve can hold pressures as high as 200 kPa without any significant leakage. Both the LAMP chamber and the valves were actuated with thin film heaters. The utility of the cassette was demonstrated by carrying out LAMP of Escherichia coli DNA target and reverse transcribed loop meditated isothermal amplification (RT-LAMP) of RNA targets. The amplicons were detected in real time with a portable, compact detector. The system was capable of detecting as few as 10 target molecules per sample in well under 1 h. The portable, integrated cassette system described here is particularly suited for applications at the point of care and in resource-poor countries, where funds and trained personnel are in short supply. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10404-011-0788-3) contains supplementary material, which is available to authorized users. |
Two new enzyme-linked immunosorbent assayes (ELISA) for the diagnosis ofBabesia bovis in cattle are described. The ELISA using a native antigen is more sensitive and less laborious than the assays described previously, because it does not require adsorption of sera with bovine erythrocytes. The second ELISA, using a recombinantB. bovis antigen expressed inEscherichia coli, was both sensitive and specific. It is suitable to replace the native antigen, thus avoiding large batch-to-batch variations in antigen preparations and the need to sacrifice experimental cattle. |
A number of different laboratories reported on studies with orally administered interferons and cytokines. Their observations extend previous observations which showed that orally administered interferons and cytokines can exert both local and systemic effects. As difficult as it may be to understand how orally administered interferons and cytokines may exert both effects, the increasing number of laboratories that demonstrate biological effects with orally administered cytokines suggests that serious consideration be given to the possibility that orally administered interferons and cytokines can indeed exert effects. They also raise the possibility that these effects may have biological relevance for the treatment of human disease. Moreover, they may indicate that the nasal/oral region is a window on the environment. It is most important, however, to assure that these experiments are performed with special care to avoid presenting preliminary data that is not properly controlled. It is essential to carry out these studies with sufficient animals or patients to ascertain their significance; and to plan the studies as double-blind evaluations to avoid misinterpretations when subjective tests are used. Nevertheless, the overall data presented give one the impression of an area that should be pursued. |
Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/−) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072–1.513, p = 0.010). No association was found between rs10774671 and MS. As the two SNPs are in linkage disequilibrium in Europeans, the previously reported association between rs10774671 and MS susceptibility might be driven by rs11352835, possibly explaining the contrasting results previously observed for the splice-site polymorphism. Thus, we describe a novel susceptibility variant for MS in OAS1 and show that population genetic analyses can be instrumental to the identification of selection targets and, consequently, of functional polymorphisms with an effect on phenotypic traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-011-1053-2) contains supplementary material, which is available to authorized users. |
Humans, animals and plants suffer from similar types of diseases (e.g., fungal, viral etc.). These can “emerge” as new diseases by expanding their geographical range or by jumping species (from plants to plants, or from animals to humans). Emerging diseases place an additional burden on developing countries which are often struggling to manage the diseases they already have. New diseases spread through weather, insects or other vectors, or by the movement of people, animals or goods. This study examines the role of cross-border travel in the spread of diseases. A survey of travelers and of residents along the Malawi-Mozambique border found that most cross it frequently and that they rarely travel empty-handed, often taking plants and animals with them. People also cross borders seeking medical attention. Attempting to limit travel would hamper an already struggling economy, where many people make a living by producing, processing or transporting plants and animals for food. Cross border travel per se may pose slight danger for the spread of diseases, if governments can collaborate on sharing information about the status of diseases within their border. |
Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. The recent flu pandemic caused by a swine-origin influenza virus A/H1N1 (S-OIV) presents an opportunity to examine virulence factors, the spread of the infection and to prepare for major influenza outbreaks in the future. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it probably arose through reassortment of two viruses of swine origin. Specific markers for virulence can be evaluated in the viral genome, PB1-F2 is a molecular marker of pathogenicity but is not present in the new S-OIV. While attention was focused on a threat of an avian influenza H5N1 pandemic emerging from Asia, a novel influenza virus of swine origin emerged in North America, and is now spreading worldwide. However, S-OIV demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. There are concerns that this virus may mutate or reassort with existing influenza viruses giving rise to more transmissible or more pathogenic viruses. The 1918 Spanish flu pandemic virus was relatively mild in its first wave and acquired more virulence when it returned in the winter. Thus preparedness on a global scale against a potential more virulent strain is highly recommended. Most isolates of the new S-OIVs are susceptible to neuraminidase inhibitors, and currently a vaccine against the pandemic strain is being manufactured and will be available this fall. This review summarizes the current information on the new pandemic swine-origin influenza virus A/H1N1. |
Development of the functionalization of triterpenoids to A-secoamidoximes, A-secomethylenamines, and branched 3-(3-aminopropylamino)-3-(3-aminopropoxy)amidoximes is illustrated by the betulonic acid ketoxime. An effective way to get of the derivatives of 20,29-dihydrolupanes using diborane is suggested. The antiviral and antituberculosis activity data of some compounds are presented. |
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