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Does society benefit from encouraging or discouraging private infectious disease-risk mitigation? Private individuals routinely mitigate infectious disease risks through the adoption of a range of precautions, from vaccination to changes in their contact with others. Such precautions have epidemiological consequences. Private disease-risk mitigation generally reduces both peak prevalence of symptomatic infection and the number of people who fall ill. At the same time, however, it can prolong an epidemic. A reduction in prevalence is socially beneficial. Prolongation of an epidemic is not. We find that for a large class of infectious diseases, private risk mitigation is socially suboptimal—either too low or too high. The social optimum requires either more or less private mitigation. Since private mitigation effort depends on the cost of mitigation and the cost of illness, interventions that change either of these costs may be used to alter mitigation decisions. We model the potential for instruments that affect the cost of illness to yield net social benefits. We find that where a disease is not very infectious or the duration of illness is short, it may be socially optimal to promote private mitigation effort by increasing the cost of illness. By contrast, where a disease is highly infectious or long lasting, it may be optimal to discourage private mitigation by reducing the cost of disease. Society would prefer a shorter, more intense, epidemic to a longer, less intense epidemic. There is, however, a region in parameter space where the relationship is more complicated. For moderately infectious diseases with medium infectious periods, the social optimum depends on interactions between prevalence and duration. Basic reproduction numbers are not sufficient to predict the social optimum. |
The recent outbreak of Ebola in West Africa has killed thousands of people, including healthcare workers. African responses have been varied and largely ineffective. The WHO and the international community’s belated responses have yet to quell the epidemic. The crisis is characteristic of a failure to properly comply with the International Health Regulations 2005. More generally, it stems from a failure of international health justice as articulated by a range of legal institutions and instruments, and it should prompt us to question the state and direction of approaches to the governance of global public health. This paper queries what might be done to lift global public health as a policy arena to the place of prominence that it deserves. It argues that there are at least two critical reasons for the past, present and easily anticipated future failings of the global public health regime. After exploring those, it then articulates a new way forward, identifying three courses of action that might be adopted in realising better health outcomes and global health justice, namely value, institutional and legal reform. |
Cytokines are a family of signaling polypeptides involved in intercellular interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. |
The current outbreak of Ebola virus infection in West Africa continues to spread. Several patients have now been treated in the United States and preparations are being made for more. Because of the strict isolation required for their care, questions have been raised about what diagnostic and therapeutic interventions should be available. I discuss the ethical challenges associated with caring for patients in strict isolation and personnel wearing bulky protective gear with reduced dexterity and flexibility, the limitations this may place on available treatments and the permissibility of consequent departures from the standards of care. Restricting access to some interventions such as surgery requiring an operating room, advanced imaging, etc. is reasonable due to concern for protecting other patients, visitors and staff. Cardiopulmonary resuscitation is a special case and the implications for withholding this intervention in situations where it may be desired is discussed, especially with respect to those patients who have suspected, but not proven, infection. These same restrictions are also considered under conditions where there are scarce resources and thus limited numbers of patients may receive care. While it is to be hoped that there is only limited and sporadic infection with Ebola virus in the US, careful thought must be given to the care of these patients under the unusual circumstances demanded by their isolation. I argue that an altered standard of care is reasonable and ethically acceptable under certain conditions. |
In France, home confinement is not a common preventive measure against an influenza pandemic, although it is used around the world. Based on a stated method approach, we analyze the attitude that the French would adopt if this measure were put in place. Next, we propose a cost–benefit analysis to discuss the cost-effectiveness of this measure. We find that over three-quarters of respondents report complying with home confinement. Their choice depends on their individual characteristics, the interaction they may have with an infected person and home confinement conditions, but not their experience with preventive measures. We find that behaviors such as sensitivity to certainty, selfishness and altruism emerge. As far as cost-effectiveness is concerned, our study shows that home confinement is a prevention path that should not be neglected and should even be prescribed. |
Complications of idiopathic pulmonary fibrosis (IPF) are responsible for a relevant proportion of the mortality. Most importantly, acute exacerbation leads to an in-hospital mortality of more than 50% with a mean survival time of only a few months. Therefore, consideration of complications in IPF is of great importance for understanding the disease and treatment planning. Furthermore, the evidence for pneumological rehabilitation in IPF has greatly increased. This resulted in specific recommendations by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for improvement in physical capacity, quality of life and symptom control. |
The changing epidemiology of vector-borne diseases represents a growing threat to human health. Contemporary surveillance systems have to adapt to these changes. We describe temporal trends and geographic origins of vector-borne diseases in Germany with regard to strengths of existing disease surveillance and to areas marked for improvement. We focused on hantavirus infection (endemic in Germany), chikungunya fever (recently emerging in Europe) and dengue fever (imported from tropical regions), representing important subgroups of vector-borne infections. Routine surveillance data on demographics, origin of infection and the date of reporting were analysed. From 2001 through 2007, 3,005 symptomatic hantavirus infections, and 85 cases of chikungunya fever were reported, similarly 1,048 cases of dengue fever in 2002 through 2007. The geographic origin of hantavirus infection was reported for 95.5% of all cases (dengue virus, 98.4%; chikungunya virus, 100%). Hantavirus infections were acquired in Germany in 97.6% of cases (n = 2800). In 2007, there was a marked increase of hantavirus cases, mainly in areas known to be endemic for hantavirus. In 2006, imported cases of chikungunya fever primarily returned from several islands of the Indian Ocean, while the majority of imported cases in 2007 came from India. The reported number of dengue fever cases have increased since 2004. Thailand contributed the largest proportion of cases (17–43% in individual years), followed by India, Brazil and Indonesia. Surveillance of notifiable vector-borne diseases in Germany is able to timely detect spatial and temporal changes of autochthonous an imported infections. Geographic and temporal data obtained by routine surveillance served as a basis for public health recommendations. In addition to surveillance of vector-borne infections in humans, nationwide monitoring programs and inventory techniques for emerging and reemerging vectors and for wildlife disease are warranted. |
Several papers in the literature employ agent-based modeling approach for providing reasonable solutions to dynamic optimization problems (DOPs). However, these studies employ a variety of agent-based modeling approaches with different strategies and features for different DOPs. On the other hand, there is an absence in the literature of a formal representation of the existing agent-based solution strategies. This paper proposes a representation scheme indicating how the solution strategies with agent-based approach can be summarized in a concise manner. We present these in a tabular form called “Agent Based Dynamic Optimization Problem Solution Strategy” (ABDOPSS). ABDOPSS distinguishes different classes of agent based algorithms (via communication type, cooperation type, dynamism domain and etc.) by specifying the fundamental ingredients of each of these approaches with respect to problem domain (problems with dynamic objective functions, constraints and etc.). This paper also analyzes 18 generic studies in the literature employing agent-based modeling based on ABDOPSS. |
The Brevinin peptides are antimicrobial agents obtained from frog skin secretions. Brevinin-2R has attracted many attentions due to its very low hemolytic activity, cationic property, and high affinity to cancer cells. Moreover, it has shown little toxicity against normal mammalian cells, while having killed several tumor cell lines by activation of lysosome-mitochondrial death pathway. In this review, we introduced the Brevinin superfamily with a focus on its therapeutic applications. Next, some unique properties of Brevinins were briefly discussed, including their ability to stimulate insulin secretion, dendritic cell maturation, and wound healing. In this context, we also provide information about the decoration of nanoparticles, such as cerium nano-oxide, by Brevinins. Finally, we addressed their potential for anti-tumor and drug design applications. |
TiO(2) photocatalysis with ultraviolet (UV-A) light has proven to be a highly effective process for complete inactivation of airborne microbes. However, the overall efficiency of the technology needs to be improved to make it more attractive as a defense against bio-terrorism. The present research investigates the enhancement in the rate of destruction of bacterial spores on metal (aluminum) and fabric (polyester) substrates with metal (silver)-doped titanium dioxide and compares it to conventional photocatalysis (TiO(2) P25/+UV-A) and UV-A photolysis. Bacillus cereus bacterial spores were used as an index to demonstrate the enhanced disinfection efficiency. The results indicate complete inactivation of B. cereus spores with the enhanced photocatalyst. The enhanced spore destruction rate may be attributed to the highly oxidizing radicals generated by the doped TiO(2). |
This paper provides for an overview on the practical consequences of the EC guideline (III/8115/89): Validation of Virus Removal and Inactivation. This guideline can only be used as a blueprint in combination with other specific guidelines, especially those concerned with EC recommendations during production and quality control for various biotech products. A potential risk associated with the production and use of biological products is viral contamination. This contamination may be present in the source material, eg. human blood, human or animal tissues, cell banks, or introduced in the manufacturing process through the use of animal sera (eg. foetal calf serum or trypsin) in cell culture supernatant. The objectives of validation are to establish — ideally both qualitatively as well as quantitatively — the overall level of virus clearance. Evidence of viral clearance must be obtained in all stages of purification and adequate viral removal and/or inactivation must be proven. The method used when validating viral removal and /or inactivation is by challenging the system through the deliberate addition (“spiking”) of significant amounts of virus into the crude material to be purified and to different fractions obtained during the various purification stages. Removal or inactivation of the virus during the subsequent stages of purification and /or inactivation is thereafter determined. Such a quality system is by no means a simple one: it is estimated that in some production lines around 600 Standard Operating Procedures are necessary to guarantee the quality and the safety of the desired biotechnological product. Small companies will probably not be able to perform all procedures needed for obtaining the desired quality of the product. Then, external laboratories may take over a part of the Part II development requirements, which may not be representative for the total of internal Quality Assurance. New developments in the production and quality control of biotechnological products may require that companies should introduce novel, sophisticated methods such as: polymerase chain reaction (PCR), as yet not recommended by the CPMP in detail. |
Messenger RNAs encoding the nitrate reductase apoenzyme from tobacco can be translated in a cell-free system. Poly(A)(+) mRNA fractions from the 23-32 S area of a sucrose gradient were used to build a cDNA library in the expression vector λgt11 with an efficiency of cloning of approximately 10(4) recombinants/ng mRNA. Recombinant clones were screened with a rabbit polyclonal antibody directed against the corn nitrate reductase, which cross reacts specifically with the nitrate reductases from dicotyledons. Among 240000 recombinant plaques, eight clones were isolated containing inserts of sizes ranging from 1.6 kb to 2.1 kb and sharing sequence homologies. Seven of these clones contained a common internal 1.6 kb EcoRI fragment. The identity of these clones was confirmed as follows. A fusion protein of 170 kDa inducible by IPTG and recognized by the rabbit nitrate reductase antibody was expressed by a lysogen derived from one of the recombinants. The antibodies binding the fused protein were eluted and shown to be inhibitory to the catalytic activity of tobacco nitrate reductase. Two monoclonal antibodies directed against nitrate reductase were also able to bind the hybrid protein. The 1.6 kb EcoRI fragment was sequenced by the method of Sanger. The open reading frame corresponding to a translational fusion with the β-galactosidase coding sequence of the vector shared strong homology at the amino acid level with the heme-binding domain of proteins of the cytochrome b5 superfamily and with human erythrocyte cytochrome b5 reductase. When the 1.6 kb EcoRI fragment was used as a probe for Northern blot experiments a signal corresponding to a 3.5 kb RNA was detected in tobacco and in Nicotiana plumbaginifolia mRNA preparations but no cross-hybridization with corn mRNAs was detected. The probe hybridized with low copy number sequences in genomic blots of tobacco DNA. |
Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was not in a severely immunocompromised state. On histological examination, only a few tiny incomplete necrotic foci were found in the subcortical area. These foci were widely dispersed. Rare, swollen oligodendroglial cells and astrocytes in which papovavirus capsid protein (VP-1) was demonstrated immunohistochemically were present around the foci. The two typical types of virus particles i.e. 35 to 40 nm round particles and elongated particles, were observed in the nuclei of the swollen glial cells. The latter were in the minority. Distinct crystals were also found in the nuclei. The centre-to-centre distance of the particles in the crystals, about 40 nm, and the electron-opaque spots of the round-shaped virions and of the elongated particles, were indicative of structural subunits of papovavirus capsids. This case provides further evidence that papovavirus, possibly JC virus, may be reactivated in the brains of aged patients who are not in an immunocompromised state. |
Heat shock protein-60 (HSP60) is implicated in several autoimmune diseases as a triggering antigen. Based on the autoimmune hypothesis of schizophrenia, we examined cellular and humoral responses against HSP60 and a series of its peptide fragments with peripheral blood samples of schizophrenic patients and healthy subjects each of group size between 12 to 32 participants. The average stimulation indices of peripheral blood mononuclear cells (PBMC) to HSP60 were 3.17 ± 0.36 (mean ± SE) for schizophrenic patients and 2.23 ± 0.24 (mean ± SE) for healthy subjects, with a significant difference between the groups (P = 0.0457). In parallel, 38 synthetic peptide fragments of HSP60, each of 18–21 amino acids, were tested for in vitro sensitization of PBMC. With one peptide (p32) the average stimulation index of PBMC from schizophrenic patients was significantly higher than that obtained for PBMC of control subjects (P = 0.0006). Comparing the cellular immune response to p32 between patients who were distinctive responders (n = 10) or non-responders (n = 10) to neuroleptic treatment indicated a similar elevation of cellular response in these groups. Antibodies against HSP60 were screened by dot-blot and ELISA in the sera of the above blood samples. Titers of IgG and IgM against HSP60 were found to be of similar magnitude in schizophrenic patients and in controls. Titers of IgA against HSP60 were somewhat higher in the sera of schizophrenic patients in comparison to sera of control subjects (P = 0.0605). |
A patient with mild choroideremia has been shown to carry a balanced translocation between chromosome X and 13 – 46,X,t(X;13)(q21.2;p12). Loci (DXY21, DX232, DX233) shown to map to this region on the X chromosome and in some cases to be deleted in other patients with choroideremia are intact in the DNA from this patient. To our knowledge this is the first report of a translocation associated with choroideremia. One of the translocation chromosomes, derivative 13, free of the derivative X and normal X, has been isolated in a somatic cell hybrid. Because of the clinical association of the eye findings with chromosome interchange, we suggest that the breakpoint on the X is at or near the choroideremia locus. Further analysis of this translocation may be useful in cloning the choroideremia gene. |
Using fusions between the Escherichia coli genes argI and lacZ, it has been demonstrated that ribosomal frameshifting occurs at a frequency of between 3% and 16% within the argl mRNA, soon after the initiation codon. The frameshift involves a phenylalanyl-tRNA shifting into the + 1 frame at the sequence UUU-U/C. The shift does not occur if the in-frame phenylalanine codon UUU is replaced by UUC. The level of frameshifting is higher in dense cultures and is not dependent on phenylalanine starvation. In the wild-type argI gene this frameshifting event would be an error, leading to a truncated, non-functional protein. Therefore, it is unlike the numerous examples of required frameshifting events that have been described in other genes. |
The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10753-014-9840-2) contains supplementary material, which is available to authorized users. |
The article opens with an overview of the relevant global crises, particularly those that have gained mainstream attention through the mass media since the 1980s. After this introduction, the facts about greenhouse gas/carbon dioxide emissions and climate change are presented and global greenhouse gas emissions are analyzed by region. This is followed by an in-depth analysis of the situation in the European Union and Austria, complemented by an explanation of the European emissions trading system. In this section, the various groups within the industrial sectors are described along with the concept of carbon leakage. In addition, the objectives of emissions trading and its impact on the prices of emissions certificates are analyzed. The article concludes by presenting alternative ideas for the reform of the emissions trading system and examining the outlook regarding the European Union’s further climate goals and their impact on Austria. |
The design of immunization strategies is an extremely important issue for disease or computer virus control and prevention. In this paper, we propose an improved local immunization strategy based on node’s clustering which was seldom considered in the existing immunization strategies. The main aim of the proposed strategy is to iteratively immunize the node which has a high connectivity and a low clustering coefficient. To validate the effectiveness of our strategy, we compare it with two typical local immunization strategies on both real and artificial networks with a high degree of clustering. Simulations on these networks demonstrate that the performance of our strategy is superior to that of two typical strategies. The proposed strategy can be regarded as a compromise between computational complexity and immune effect, which can be widely applied in scale-free networks of high clustering, such as social network, technological networks and so on. In addition, this study provides useful hints for designing optimal immunization strategy for specific network. |
Acute promyelocytic leukemia, a form of acute myeloid leukemia, is characterized by cell differentiation arrest at the promyelocyte stage. Current therapeutic options include administration of all trans-retinoic acid (ATRA), but this treatment produces many side effects. ATRA is known to induce differentiation of leukemic cells into granulocytes, but the mechanism of this process is poorly studied. We performed comparative proteomic profiling of HL-60 promyelocytic cells at different stages of ATRA-induced differentiation to identify differentially expressed proteins by high-resolution mass spectrometry and relative quantitative analysis without isotope labels. A total of 1162 proteins identified by at least two unique peptides were analyzed, among them 46 and 172 differentially expressed proteins were identified in the nuclear and cytosol fractions, respectively. These differentially expressed proteins can represent candidate targets for combination therapy of acute promyelocytic leukemia. |
Temporality should be considered in the design of information technology support for crisis management (CM), both because crises are dynamic events and because time is a part of situation awareness (SA). This study has used group interviews to explore how different temporal aspects of CM can be considered in CM design and how they can influence crisis managers SA. A prototype and a scenario were used as mediating materials. The result consists of two parts. The first part is comprised of the participants’ reflections on how timelines can be used to display information in CM information systems. According to the participants, timelines should present: deadlines, information sent to the public, incoming and outgoing information, an overview of where the current activities belong in the CM process and what has been going on since the last shift during shift changes. Timelines should not only display the listed information, but also provide functionality for adjusting the timescale so that information can be presented in alternative temporal perspectives. The second part of the result contains several obstacles that might influence the crisis managers’ ability to obtain SA. Obstacles elicited from the group discussions are: information overflow, fast changes of SA due to incoming information, difficulties to share SA with actors outside the CM centre, forgetting things that need attention and that SA depends on the quality of incoming information. The two parts of the result have been compiled into six design principles for how temporality can be considered in CM systems in order to support SA. |
In a search for novel antiviral compounds of the ‘doubly modified’ nucleoside type, we have prepared 1-(4-hydroxy-2-oxabutyl)-, 1-(4-hydroxy-3-hydroxymethyl-2-oxabutyl)-, 1-(4-hydroxy-1-hydroxymethy1-2-oxabutyl)-, 1-(4-hydroxy-1-methyl-2-oxabutyl), 1-(4,5-dihydroxy-2-oxapentyl)-, 1-(5-hydroxy-2-oxapentyl), 1-(5-hydroxy-1-chloromethyl-2-oxapentyl)-, and 1-(6-hydroxy-1-chloromethyl-2-oxahexyl)-2-(trifluoromethylthiomethyl)benzimidazole. They were obtained by condensing the trimethylsilyl derivative of 2-(trifluoromethylthiomethyl) benzimidazole with alkylating agents in the presence of an equimolar mixture of trifluoromethanesulfonic acid and trimethylchlorosilane. These nucleoside analogs showed moderate antiviral activity against some RNA viruses. |
Intracellular protein distribution and sorting were examined in rat parotid striated duct cells, in which tissue kallikrein is apical, and Na,K-ATPase is basolateral. Electron-microscopic immunogold cytochemistry, with both polyclonal and monoclonal antibodies, demonstrated these enzymes at opposite poles of the cells and in distinct intracellular sites. Kallikrein was found within apical secretory granules, whereas Na,K-ATPase was present on basolateral cell membranes. In addition, kallikrein was localized throughout cisternae of all Golgi profiles, whereas Na,K-ATPase (α-subunit) was found only in small peripheral vesicles and/or lateral cisternal extensions of a basal subset of Golgi profiles. These differences in the subcellular distribution of the two marker antigens were most clearly seen with double immunogold labelling. Our results suggest that kallikrein, an apical, regulated secretory protein, and Na,K-ATPase, a basolateral, constitutively transported membrane protein, are segregated at (or prior to) the level of the Golgi apparatus rather than in the trans-Golgi network (TGN), as was expected. |
1-(2,3-Dihydroxypropyl)-, 1-(4-hydroxy-2-oxabutyl)-, 1-(3-hydroxymethyl-4-hydroxy-2-oxabutyl)-, 1-(1,5-dihydroxy-3-oxa-2-pentyl)-, 1-(5-hydroxy-3-oxa-2-pentyl)-, and 1-(4,5-dihydroxy-2-oxapentyl)-2-trifluoromethyl- and -2-trifluoromethylthiobenzimidazoles were obtained by condensation of trimethylsilyl derivatives of 2-substituted benzimidazoles with alkylating agents in the presence of SnCl(4), or by direct alkylation of the sodium salts of the heterocycles. |
The ability to explicitly represent infectious disease distributions and their risk factors over massive geographical and temporal scales has transformed how we investigate how environment impacts health. While landscape epidemiology studies have shed light on many aspects of disease distribution and risk differentials across geographies, new computational methods combined with new data sources such as citizen sensors, global spatial datasets, sensor networks, and growing availability and variety of satellite imagery offer opportunities for a more integrated approach to understanding these relationships. Additionally, a large number of new modelling and mapping methods have been developed in recent years to support the adoption of these new tools. The complexity of this research context results in study-dependent solutions and prevents landscape approaches from deeper integration into operational models and tools. In this paper we consider three common research contexts for spatial epidemiology; surveillance, modelling to estimate a spatial risk distribution and the need for intervention, and evaluating interventions and improving healthcare. A framework is proposed and a categorization of existing methods is presented. A case study into leptospirosis in Sri Lanka provides a working example of how the different phases of the framework relate to real research problems. The new framework for geocomputational landscape epidemiology encompasses four key phases: characterizing assemblages, characterizing functions, mapping interdependencies, and examining outcomes. Results from Sri Lanka provide evidence that the framework provides a useful way to structure and interpret analyses. The framework reported here is a new way to structure existing methods and tools of geocomputation that are increasingly relevant to researchers working on spatially explicit disease-landscape studies. |
Duchenne muscular dystrophy (DMD) is a genetic X-linked recessive orphan disease that affects approximately 1 in 3 500 male births. Boys with DMD have progressive and predictable muscle destruction due to the absence of dystrophin, a protein present under the muscle fiber membrane. This absence induces contraction-related membrane damage and activation of inflammatory necrosis and fibrosis, leading to cardiac/diaphragmatic failure and death. The authors support the therapeutic role of myoblast transplantation in DMD, and describe the history and rationale for such an approach. |
ABSTRACT: New series of Schiff’s bases, hydrazones, thiosemicarbazones, thiazoles, and thiocarbohydrazones of 5-fluoroisatin were synthesized by the reaction of 5-fluoroisatin with primary amines, hydrazine hydrate, and thiocarbohydrazides. Thiosemicarbazones were prepared by reacting hydrazone derivatives with isothiocyanates. Upon treatment of thiosemicarbazone derivatives with chloroacetone, the thiazole derivatives were obtained. Some of the prepared compounds exhibited antiviral activity. GRAPHICAL ABSTRACT: [Image: see text] |
The human MxA protein, encoded by the interferon-inducible MX1 gene, is an intracellular influenza A virus (IAV) restriction factor. It can protect transgenic mice from severe IAV-induced disease, indicating a key role of human MxA for host survival and suggesting that natural variations in MX1 may account for inter-individual differences in disease severity among humans. MxA also provides a robust barrier against zoonotic transmissions of avian and swine IAV strains. Therefore, zoonotic IAV must acquire MxA escape mutations to achieve sustained human-to-human transmission. Here, we discuss recent progress in the field. |
Threatened use of the smallpox virus in bioterrorist attacks recently prompted national concerns in the United States. Smallpox, the “speckled monster,” was known in antiquity. In 1856, New York City opened its first hospital devoted to caring for victims of smallpox. Essentially, the hospital isolated and quarantined patients on Blackwell’s Island, located in the East River between Manhattan and Queens. After the hospital closed about 1875, the facility became a training school for female and male nurses. In the mid 1950s, the building was abandoned. Today, the ruins of the smallpox hospital are listed on the National Register of Historic Places. At night, the ruins are illuminated casting an eerie, green aura on the remaining stone walls. |
A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4–37.6 vs 21.6–25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU. |
A 70-year-old woman with secretory diarrhea was studied with a novel technique of recording small intestinal myoelectrical activity which allowed us to obtain long, uninterrupted records of slow waves and spikes at eight or more different intestinal levels simultaneously. Typical migrating action potential complexes (MAPCs) were observed, consisting of spike bursts that extended over more than one slow wave and migrated distally at the same propagation velocity as the slow waves. This motility pattern occurred frequently during the period the patient presented with secretory diarrhea and disappeared with the disappearance of the diarrhea. It was observed only once in a series of 10 normal control subjects. This is the first report on MAPC activity in man and on the association of this myoelectrical pattern with secretory diarrhea in man. |
Currently available prognostic tools are inadequate to discern the molecular basis of the heterogenic response in hepatitis C virus (HCV)-infected patients treated with the current standard of therapy. The expression and biological function of immune mediators have been shown to be critical in all phases of the immune response to HCV infection and likely therefore influence host response. Herein, a biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effects of host response in 10 HCV patients. Serum levels of 17 cytokines were compared before and after 1 month of treatment and against controls. Overall serum cytokine levels were significantly higher in patients (P < 0.05) than controls. Additionally, viral titers decreased in all patients after 1 month of therapy, as did overall serum cytokine levels in the cohort (P < 0.05). To assess relationships between changes in cytokine levels and changes in viral titer, the cohort was divided into three statistically distinct subgroups based on changes in viral titers. Specific sets of cytokines decreased in each group: decreases in CCL4, interleukin (IL)-2, CXCL8, and IL-1β correlated with the greatest drops in viral titer, decreases in IL-5, granulocyte colony stimulating factor (G-CSF), and CCL4 correlated with moderate drops in viral titer, and only CCL2 correlated with the lowest drops in viral titer. Interestingly, decreases in CCL4 levels correlated with decreases in viral titers in all patients. CCL4 controls leukocyte influx and thus propagates inflammation. In conclusion, these data raise the possibility that characteristic changes in host response modulate the therapeutic response, demonstrating the prognostic power of serum cytokine profiling in chronic HCV. |
The purpose of this paper is to examine current health care literature (1980–2000) regarding the microbiology of the home environment, to summarize evidence of transmission within the home, and to assess effectiveness of cleaning practices and products. The home environment, particularly the kitchen and bathroom, serves as a reservoir of large numbers of microorganisms, particularly Enterobacteriacae,and infectious disease transmission has been demonstrated to occur in 6–60% of households in which one member is ill. Current food preparation and cleaning practices provide multiple opportunities for intra-household member spread. Routine cleaning is often sufficient, but in cases of household infection, may not adequately reduce environmental contamination. The effectiveness of disinfectants varies considerably and depends on how they are used as well as their intrinsic efficacy. The behavioral aspects of infection prevention in the home (e.g., foodhandling and cleaning practices) warrant increased public attention and education. |
Race and ethnicity are well-established epidemiological categories that relate to the patients’ risk of exposure and their susceptibility/resistance to disease. However, this association creates the notion that factors other than a personal identity need not be held responsible for patients’ health problems. This work deconstructs the notion of race and ethnicity as risk factors for immigrant ill health, which is prevalent in current medical research and practice, by tracing its roots in Canadian history. The understanding that medical knowledge is subject to diverse historical, social, cultural and political influences can change the way health professionals perceive their patients as a health threat. |
1. In order to characterize some of the molecular events leading to repair of myelin in the adult central nervous system (CNS), we examined the expression of transcripts for myelin basic protein (MBP) during remyelination in the mouse. C57B1/6 mice develop a demyelinating disease when glial cells are selectively infected by the A59 strain of mouse coronavrius. The virus is spontaneously cleared from the mice by 4 weeks postinfection (WPI), a time when remyelination is starting. 2. At 3 WPI total MBP transcripts are decreased by 75% in demyelinating lesions compared to control white matter. Using RNase protection assays andin situ hybridization with probes for particular MBP exons, we detected an increase in MBP transcripts containing exon 2 information, coincident with the earliest histological signs of remyelination. 3. The expression of MBP transcripts containing exon 2 information was first seen clustered in the perinuclear cytoplasm of oligodendrocytes scattered within the lesions. This is reminiscent of the increased levels and perinuclear clustering of MBP transcripts containing exon 2 seen during early developmental myelination. The peak abundance of exon 2-containing transcripts in the lesions was 13-fold that seen in control white matter. At later stages of remyelination, additional forms of MBP transcripts (without exon 2) increased and their distribution was more diffuse. 4. Thus, during remyelination, preforms of MBP transcripts, which are normally present at low levels in the adult CNS, are abundantly expressed and regulated in a manner similar to that observed in developmental myelination. |
• Background: Subacute viral infection is known to change the phenotype of infected cells, thereby causing immune-mediated tissue damage. The aim of this study was to investigate the expression of different cell surface molecules on human retinal pigment epithelial cells (RPEC) following viral infection, with special emphasis on those having immuneregulatory functions. • Methods: Cultured RPEC were infected with cytomegalovirus (CMV), coxsackievirus B3 (CVB) or herpes simplex virus type I (HSV). Double-staining fluorescence technique was used for visualization of virus infection and cell surface markers in the same cells by laser microscopy. • Results: CMV down-regulated MHC class I antigens on RPEC, whereas CVB and HSV did not alter MHC class I antigen expression. No induction of class 11 antigens was observed in RPEC infected with CVB, HSV or CMV. The intercellular adhesion molecule ICAM-1 (CD54) was strongly expressed in uninfected RPEC, and a slight increase was observed after virus infection. Vascular cell adhesion molecule 1 (VCAM-1) was expressed in low amounts in both uninfected and infected RPEC. No expression of intercellular adhesion molecule 2 (ICAM-2), E-selectin ELAM-1 or lymphocyte-function-associated antigen 1 (LFA-1) was observed on RPEC before or after virus infection. • Conclusion: Down-modulation of immune-regulating cell surface antigens has been suggested to provide a means of long-term survival of viruses in the infected cell, favoring establishment of persistent infection. Our observation in cultured human RPEC indicates that this mechanism might indeed contribute to the development of disease affecting retinal tissue. |
BACKGROUND: Aldosterone induces inflammation and fibrosis in the kidney, while nuclear factor κB (NFκB) plays key roles in inflammation mediated by various cytokines. Here, we determined the roles of NFκB activation in aldosterone-induced kidney injury. METHODS: We used unilaterally nephrectomized rats with or without continuous aldosterone infusion and 0.9% saline as drinking water for 3 weeks. IMD-1041, an IKKβ inhibitor, and spironolactone were orally administered to inhibit NFκB and mineralocorticoid receptor, respectively. RESULTS: The aldosterone-infused rats exhibited severe kidney injury, hypertension, and increased expression of pro-inflammatory and fibrotic proteins, osteopontin, fibrinogen, collagen type I, and PAI-1. Western blotting confirmed NFκB activation by aldosterone by the increased amount of p65 in the nuclear fraction of the kidney, and oral IMD-1041 prevented the kidney injury and lessened the increase in pro-inflammatory and fibrotic proteins without significant changes in blood pressures. In addition, changes in angiotensin-converting enzyme 2 (ACE2), which has been found to act as a protective factor in various kidney injury models, were examined. Immunofluorescence studies revealed the presence of ACE2 in the brush-border membrane of the proximal convoluted tubules and markedly blunted ACE2 staining in aldosterone-infused rats. The decrease in amount of ACE2 protein was confirmed by Western blotting, and IMD-1041 also prevented the decrease in ACE2. The administration of spironolactone also abolished the effects of aldosterone. CONCLUSION: Our results suggest that aldosterone induces kidney injury via activation of NFκB and mineralocorticoid receptor, and that decreased ACE2 expression may play an important role in aldosterone-induced kidney injury. |
We report a functional and molecular analysis of nine oncocytic tumors of the human thyroid. In all the abundance of mitochondria observed ultrastructurally was accompanied by an increase in enzymatic activities of respiratory complexes I (NADH dehydrogenase), II (succinate dehydrogenase) IV (cytochrome c oxidase), and V (ATPase). Western blot analysis failed to detect uncoupling protein in the tumors. The elevated respiratory enzyme activities were paralleled by an increase in the mitochondrial DNA content. Restriction analysis of mitochondrial DNA gave no indication of heteroplasmy or other gross alterations. We conclude that the mitochondrial proliferation in oncocytic tumors is probably not the result of a compensatory mechanism for the deficiency in enzyme complexes of the mitochondrial respiratory chain. |
Signal transduction across biological membranes is modulated by a family of related GTP-binding proteins termed G proteins. These G proteins have a heterotrimeric structure composed of α, β, and γ subunits. The α subunits of the G proteins bind GTP and appear to determine the biochemical specificity of the protein. We have recently cloned and characterized cDNA encoding two G-protein α subunits, α(i) and α(h). The former is a substrate for ADP-ribosylation by pertussis toxin. The protein corresponding to α(h) has not yet been identified. These cDNAs encode proteins, which demonstrate 90% sequence identity to one another and also show marked similarity to other G proteins. The present studies were designed to determine whether the genes for these related proteins are clustered on a single human chromosome. Genomic DNA isolated from a panel of mouse-human hybrid cell lines was analyzed by hybridization to cDNAs for α(i) and α(h). Based on the distribution patterns of α(i) and α(h) in cell hybrids, the gene for α(i) was assigned to human chromosome 7, and the gene for α(h) assigned to chromosome 12. These data suggest that the G-protein gene family may be distributed over at least two human chromosomes. |
The aim of this study was to collect and identify airborne bacteria in Norway, Sweden and Finland and to compare three different technologies for identifying collected airborne bacterial isolates: the “gold standard” method 16S rDNA sequencing, MALDI-TOF MS using the MALDI Biotyper 2.0 and the MIDI Sherlock(®) Microbial Identification System (MIDI MIS system). Airborne bacteria were collected during three different periods from May to October 2009 using air sampling directly on agar plates. A total of 140 isolates were collected during three sampling campaigns, and 74 % (103) of these isolates were analyzed by all three methods. The dominant genera in Norway and Finland were the gram-positive bacteria Bacillus and Staphylococcus, whereas the gram-negative bacterium Acinetobacter was the dominant genus in Sweden. Using 16S rDNA sequencing, MALDI-TOF MS and MIDI MIS analysis, 83, 79 and 75 %, respectively, of the isolates were identified and assigned to order or higher taxonomic levels. In this study, the MALDI-TOF MS combining with the MALDI Biotyper 2.0 classification tool was demonstrated to be a fast and reliable alternative for identifying the airborne bacterial isolates. These studies have increased knowledge about the airborne bacterial background in outdoor air, which can be useful for evaluating and improving the operational performance of biological detectors in various environments. To our knowledge, this is the first time that 16S rDNA sequencing, MALDI-TOF MS and MIDI MIS analysis technologies have been compared for their efficiency in identifying airborne bacteria. |
Field trials were conducted using an inactivated rotavirus vaccine for prevention of calf neonatal diarrhea. For the trials, 458 pregnant cows from 26 herds were involved. In each herd, cows which had been inseminated within a period of two months were selected and randomly subdivided in two groups. Cows in one group (248 head in total) were vaccinated 6 weeks before calving and again 4 weeks later; cows in the other group (210 head in total) were left as unvaccinated controls. At calving, colostrum was collected from each cow and stored at -30°C until used for feeding calves. The newborn calves, beginning the second day of life and for the next 7–10 consecutive days, each was fed a daily supplement of 400 ml of colostrum from its dam. The diarrhea occurred in 86 (40.9%) calves that had received colostrum from unvaccinated dams (normal colostrum), and in 7 (2.8%) calves which were fed colostrum from vaccinated dams (immune colostrum). The disease was very severe in the normal colostrum-fed calves and 52 of them died. Those calves which survived the disease underwent a significant loss of condition. By contrast, the 7 immune colostrum-fed calves displayed a rather mild enteric condition, and all recovered without any sequela being observed. |
Many emerging infectious diseases in human populations are associated with zoonotic origins. Attention has often focused on wild animal reservoirs, but most zoonotic pathogens of recent concern to human health either originate in, or are transferred to, human populations from domesticated animals raised for human consumption. Thus, the ecological context of emerging infectious disease comprises two overlapping ecosystems: the natural habitats and populations of wild animals, and the anthropogenically controlled habitats and populations of domesticated species. Intensive food animal production systems and their associated value chains dominate in developed countries and are increasingly important in developing countries. These systems are characterized by large numbers of animals being raised in confinement with high throughput and rapid turnover. Although not typically recognized as such, industrial food animal production generates unique ecosystems—environments that may facilitate the evolution of zoonotic pathogens and their transmission to human populations. It is often assumed that confined food animal production reduces risks of emerging zoonotic diseases. This article provides evidence suggesting that these industrial systems may increase animal and public health risks unless there is recognition of the specific biosecurity and biocontainment challenges of the industrial model. Moreover, the economic drivers and constraints faced by the industry and its participants must be fully understood in order to inform preventative policy. In order to more effectively reduce zoonotic disease risk from industrial food animal production, private incentives for the implementation of biosecurity must align with public health interests. |
As the human lung is exposed to a variety of microbial pathogens in the environment, a first line of defense is built up by pulmonary cells like bronchial/alveolar epithelial cells and alveolar macrophages. These cells express several pattern recognition receptors (PRRs) recognizing highly conserved microbial motifs and initiating the production of chemokines and pro- and anti-inflammatory cytokines acting as transmembrane or intracellular receptors. This might not only lead to acute but also to chronic inflammation which is discussed as an underlying mechanism in the pathogenesis of different lung diseases. |
In this study inflammatory responses were determined in rat lungs 0, 1, 3, and 8 days following single 2- and 4-hr exposures to 1.8 ppm ozone. Analysis of lavage fluid immediately following exposure demonstrated enhanced lactate dehydrogenase activity and decreased numbers of lavageable macrophages but no alterations in albumin content. Similar analyses at one day postexposure demonstrated 282% and 456% increases in albumin content and enhanced numbers of lavageable neutrophils from a control value of 0.01 ± 0.01 to 0.27 ± 0.10 and 0.78 ± 0.11 million cells per lung for 2-hr and 4-hr exposures, respectively. The observed increased levels of albumin were also present at 3 days, at which time the number of lavageable neutrophils was not significantly different than control. At both one and 3 days postexposure, lavageable lymphocytes were significantly increased 10-fold from a control value of 0.03 ± 0.01 million cells per lung. However, the number of lavageable macrophages was unaltered on day 1, but enhanced on day 3, giving values of 0.67 ± 0.05 (control), 2.25 ± 0.46 (2 hr), and 2.70 ± 1.05 (4 hr) million cells per lung. By 8 days both inflammatory cell numbers and albumin levels had returned to control values. Since these data demonstrated different time courses for each inflammatory cell type, this reversible model of acute lung injury should be useful for establishing possible involvement of these cells in processes of lung injury. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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