title: Recombinant IgA Antibodies

text: The production of monoclonal antibodies and the development of recombinant antibody technology have made antibodies one of the largest classes of drugs in development for prophylactic, therapeutic and diagnostic purposes. Currently, all of the Food and Drug Administration (FDA)- approved antibodies are immunoglobulin Gs (IgGs). However, more than 95%of the infections are initiated at the mucosal surfaces, where IgA is the primary immune effector antibody.


title: 4 Respiratoire spoedgevallen

text: Het gebruik van de term ‘status asthmaticus’ voor een ernstige, levensbedreigende astma-aanval schept veel onduidelijkheid. De ene auteur geeft hiermee een bepaalde ernst van bronchusobstructie aan, de andere verdisconteert in dit begrip de duur van een aanval, eventuele complicaties of een zekere mate van therapieresistentie.


title: Development of Mucosal Vaccines Based on Lactic Acid Bacteria

text: Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed.


title: Concepts and Theories of Longevity

text: This chapter is concerned with the concepts, statistics, theories, and future levels of human longevity, particularly extreme longevity. The term, extreme longevity or superlongevity, is used here to refer to centenarians, that is, persons with a verified age of 100 years or more. Among these we identify for special attention a subgroup known as supercentenarians, that is, persons with a verified age of 110 years or more. In both popular and scientific reporting, people aged 85 years and over have often been considered as extreme aged, but the rapid increase in the number of people in these older age groups suggests a redefinition of the notion of extreme aged. Persons in the broad age group 85 years and over are also referred to as persons of advanced age and the oldest-old. The former description now seems appropriate but the latter one does not. Preferences vary among demographers and gerontologists as to the choice of designations for these groups.


title: Virus–Platelet Associations

text: Virus–platelet interplay is complex. Diverse virus types have been shown to associate with numerous distinct platelet receptors. This association can benefit the virus or the host, and thus the platelet is somewhat of a renegade. Evidence is accumulating to suggest that viruses are capable of entering platelets. For at least one type of RNA virus (dengue virus), the platelet has the necessary post-translational and packaging machinery required for production of replicative viral progeny. As a facilitator of immunity, the platelet also participates in eradicating the virus by direct and indirect mechanisms involving presentation of the pathogen to the innate and adaptive immune systems, thus enhancing inflammation by release of cytokines and other agonists. Virus-induced thrombocytopenia is caused by tangential imbalance of thrombopoeisis, autoimmunity, and loss of platelet function and integrity.


title: 11 Longziekten

text: Deze aandoeningen, die soms met ‘verkoudheid’ of ‘griep’ betiteld worden, doen zich regelmatig – en vaak epidemisch – voor; bij kinderen (drie- tot viermaal per jaar) vaker dan bij volwassenen (een- tot tweemaal per jaar).


title: Biomedicines as Adverse Event Inducers

text: Biomedicines are new agents with old roots. Products of biological origin, such as vaccines, blood and serum components, human proteins, hormones, and immunoglobulins, are used from long time in human therapy.


title: Behavioural and Medical Differentials of Cognitive Decline and Dementia in Dogs and Cats

text: Cognitive dysfunction syndrome (CDS) is a diagnosis of exclusion given that there is no specific diagnostic test or tool and that medical disorders can cause the same set of signs. The veterinary surgeon must first identify that signs are present, collect a full history and then perform a full physical examination and relevant diagnostic tests to rule out medical causes for the signs including blood and urine analysis, radiographs and diagnostic imaging such as magnetic resonance imaging (MRI) where indicated.


title: Air Pollution and Disasters

text: Many disasters lead to air pollution and vice versa. This chapter elaborates major air pollution issues due to earthquake, tsunami, volcanic eruption, epidemics, extreme temperature, insect infestation, mass movement, wars, and fire accidents.


title: Mycobacterial Sepsis and Multiorgan Failure Syndrome

text: Tuberculosis (TB) is a global disease with high prevalence in developing countries. According to the World Health Organization (WHO) fact sheet 2009, more than 2 billion (equal to one third of world’s population) people are infected with TB bacilli. Of the cases detected, 5 % were cases of multi-drug resistant TB. Admission to a critical care unit is not required in the majority of cases. However, TB sepsis is a rapidly fatal disease that requires intensive care unit (ICU) admission and management and represents a big diagnostic and therapeutic challenge.


title: Temporal Features in Biological Warfare

text: No matter how prepared a population may be, bioterrorism cannot be prevented: the first clues will always be given by ill people. Temporal analysis applied to this type of scenarios could be an additional tool for limiting disruption among civilians allowing for recognizing typical temporal progression and duration of symptoms in first infected people. We propose the application of a fuzzy temporal reasoning system we have developed for biomedical temporal data analysis in different scenarios after a hypothetical attack. The system is able to handle both qualitative and metric temporal knowledge affected by vagueness and uncertainty, taking into account in this way the vagueness of patients reports expressed in natural language.


title: Cough, Cold, and Congestion

text: The common cold is a benign, self-limited, acute viral infection with associated symptoms of sneezing, rhinorrhea, nasal congestion, cough, and malaise. It is the most frequent acute illness in the industrialized world. Adults typically have two to three episodes of illness yearly while children can have up to five. The common cold is typically caused by viruses (including rhinovirus, RSV, coronavirus, and others), and often, no infecting organism is detected. Treatment is usually targeted at symptomatic relief. The differential diagnosis for cough, cold, and congestion is broad: ranging from non-emergent causes such as rhinitis to life-threatening illnesses such as pulmonary embolism. Careful assessment is necessary as misidentification can lead to inappropriate discharge of potentially lethal conditions.


Infection Control Methods


title: Ontology Evolution: MEDLINE Case Study

text: With the rising importance of knowledge interchange, many industrial and academic applications have adopted ontologies as their conceptual backbone. Business dynamics and changes in the operating environment often give rise to continuous changes in application requirements that may be fulfilled only by changing the underlying ontologies. This is especially true for Semantic Web applications, which are based on heterogeneous and highly distributed information resources and therefore need efficient mechanisms to cope with changes in the environment. In our previous work we have developed the KAON ontology evolution framework that (i) enables handling the required ontology changes; (ii) ensures the consistency of the underlying ontology and all dependent artefacts; (iii) supports the user to manage changes more easily; and (iv) offers advice to the user for continual ontology reengineering. In this paper we apply the proposed approach on the MEDLINE system and discuss its benefits. First, we translated the MeSH/MEDLINE into a set of the ontologies by enriching the MeSH vocabulary with the set of rules and by eliminating some inconsistencies. Second, we showed that ontology evolution ensures the consistency between all related data. Third, we indicated how formal semantics provided by an ontology might be useful to improve the indexing in the existing MEDLINE system.


title: Immunosenescence Modulation by Vaccination

text: A decline in immune function is a hallmark of aging that leads to complicated illness from a variety of infectious diseases, cancer and other immune-mediated disorders, and may limit the ability to appropriately respond to vaccination. How vaccines might alter the senescent immune response and what are the immune correlates of protection will be addressed from the perspective of (1) stimulating a previously primed response as in the case of vaccines for seasonal influenza and herpes zoster, (2) priming the response to novel antigens such as pandemic influenza or West Nile virus, (3) vaccination against bacterial pathogens such as pneumococcus and pertussis, (4) vaccines against bacterial toxins such as tetanus and Clostridium difficile, and (5) vaccine approaches to mitigate effects of cytomegalovirus on immune senescence. New or improved vaccines developed over recent years demonstrate the considerable opportunity to improve current vaccines and develop new vaccines as a preventive approach to a variety of diseases in older adults. Strategies for selecting appropriate immunologic targets for new vaccine development and evaluating how vaccines may alter the senescent immune response in terms of potential benefits and risks in the preclinical and clinical trial phases of vaccine development will be discussed.


title: Document Re-ranking by Generality in Bio-medical Information Retrieval

text: Document ranking is an important process in information retrieval (IR). It presents retrieved documents in an order of their estimated degrees of relevance to query. Traditional document ranking methods are mostly based on the similarity computations between documents and query. In this paper we argue that the similarity-based document ranking is insufficient in some cases. There are two reasons. Firstly it is about the increased information variety. There are far too many different types documents available now for user to search. The second is about the users variety. In many cases user may want to retrieve documents that are not only similar but also general or broad regarding a certain topic. This is particularly the case in some domains such as bio-medical IR. In this paper we propose a novel approach to re-rank the retrieved documents by incorporating the similarity with their generality. By an ontology-based analysis on the semantic cohesion of text, document generality can be quantified. The retrieved documents are then re-ranked by their combined scores of similarity and the closeness of documents’ generality to the query’s. Our experiments have shown an encouraging performance on a large bio-medical document collection, OHSUMED, containing 348,566 medical journal references and 101 test queries.


title: HIV/AIDS Related Respiratory Diseases

text: Lungs are the most commonly involved organ by HIV/AIDS related diseases, and pulmonary infections are the main reasons for the increasing death rate from AIDS. Pathogens of HIV related pulmonary infections include parasites, fungi, mycobacteria, viruses, bacteria and toxoplasma gondii. According to international reports, pathogens have different geographical distribution, which is also closely related to the socioeconomic status of the region to produce varied AIDS related diseases spectra. For instance, in the United States, pneumocystis carnii pneumonia (PCP), tuberculosis and recurrent bacterial pneumonia (at least twice within 1 year) occur frequently in HIV infected patients. An international report published 10 years ago indicated that PCP is the most common and serious pulmonary opportunistic infections in HIV infected patients. Now its incidence has dropped with the application of antiretroviral treatment and preventive measures. PCP will continue to occur initially in patients who are aware of their HIV infection. In addition, HIV related viral and parasitic infections have been reported both domestically and internationally. In this section, the clinical manifestations and imaging findings of HIV related pulmonary infections are analyzed and discussed, which provide effective diagnosis basis, so as to reduce the incidence of HIV-related pulmonary infections.


title: Immune Tolerance in Autoimmune Central Nervous System Disorders

text: Multiple sclerosis (MS) afflicts genetically predisposed individuals and is associated with T lymphocyte-mediated damage to the myelin sheath of neurons in the central nervous system, resulting in severely impaired signal transmission. The mechanisms of the induction and manifestation of MS are not entirely understood. The control of autoimmune disorders is accomplished by both central tolerance in which autoreactive T lymphocytes are eliminated in the thymus and by tolerance mechanisms that operate in the periphery. Among the many mechanisms described, T regulatory (Treg) cells derived from the thymus (tTregs) and induced (iTregs) in the periphery as well as T regulatory type 1 cells (Tr1) are involved in many disease models. However, the precise details of the generation and perpetuation of these various Treg subsets and their relevance to the regulation of autoimmune diseases remain elusive. In this review, we critically analyze the current knowledge of the tolerance mechanisms involved in the regulation of MS and its animal model, experimental autoimmune encephalomyelitis.


title: Step 3 of EBP: Part 1—Evaluating Research Designs

text: Step 3 of the EBP process involves evaluating the quality and client relevance of research results you have located to inform treatment planning. While some useful clinical resources include careful appraisals of research quality, clinicians must critically evaluate the content both included in these summaries and what is excluded or omitted from them. For individual research studies, clinicians must first identify and evaluate the research designs and methods reported. The terminology used to describe research designs in EBM/EBP may not always be consistent with that used in most social work research courses. This chapter provides a review of the key research designs used in EBM and EBP in order to orient clinicians to core terminology found in EBP summaries and reports.


title: A Comparison of Evolutionary Approaches to the Shortest Common Supersequence Problem

text: The Shortest Common Supersequence problem is a hard combinatorial optimization problem with numerous practical applications. Several evolutionary approaches are proposed for this problem, considering the utilization of penalty functions, GRASP-based decoders, or repairing mechanisms. An empirical comparison is conducted, using an extensive benchmark comprising problem instances of different size and structure. The empirical results indicate that there is no single best approach, and that the size of the alphabet, and the structure of strings are crucial factors for determining performance. Nevertheless, the repair-based EA seems to provide the best performance tradeoff.


Prevention and Therapy from Contact Dermatitis (with Special Reference to Occupational Dermatology)


title: RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders: Status and Challenges

text: The current status and challenges of RNA interference (RNAi) and microRNA modulation strategies for the treatment of myocardial disorders are discussed and related to the classical gene therapeutic approaches of the past decade. Section 2 summarizes the key issues of current vector technologies which determine if they may be suitable for clinical translation of experimental RNAi or microRNA therapeutic protocols. We then present and discuss examples dealing with the potential of cardiac RNAi therapy. First, an approach to block a key early step in the pathogenesis of a virus-induced cardiomyopathy by RNAi targeting of a cellular receptor for cardiopathogenic viruses (Section 3). Second, an approach to improve cardiac function by RNAi targeting of late pathway of heart failure pathogenesis common to myocardial disorders of multiple etiologies. This strategy is directed at myocardial Ca(2+) homeostasis which is disturbed in heart failure due to coronary heart disease, heart valve dysfunction, cardiac inflammation, or genetic defects (Section 4). Whereas the first type of strategies (directed at early pathogenesis) need to be tailor-made for each different type of pathomechanism, the second type (targeting late common pathways) has a much broader range of application. This advantage of the second type of approaches is of key importance since enormous efforts need to be undertaken before any regulatory RNA therapy enters the stage of possible clinical translation. If then the number of patients eligible for this protocol is large, the actual transformation of the experimental therapy into a new therapeutic option of clinical importance is far more likely to occur.


title: Nanomicrobiology

text: Microbiology plays an important role in practice of medicine. Nanodiagnostics have refined the detection of infectious diseases and many new nanotechnology-based therapies, particularly of viral diseases, are in development.


title: Dark scenarios

text: In this chapter, we present four “dark scenarios” that highlight the key socio-economic, legal, technological and ethical risks to privacy, identity, trust, security and inclusiveness posed by new AmI technologies. We call them dark scenarios, because they show things that could go wrong in an AmI world, because they present visions of the future that we do not want to become reality. The scenarios expose threats and vulnerabilities as a way to inform policy-makers and planners about issues they need to take into account in developing new policies or updating existing legislation. Before presenting the four scenarios and our analysis of each, we describe the process of how we created the scenarios as well as the elements in our methodology for analysing the scenarios.


title: Preparation Without Panic: A Comprehensive Social Marketing Approach to Planning for a Potential Pandemic

text: In recent times the world has faced several potential pandemics – SARS, avian (bird) flu, swine flu, and most recently Ebola. The risk of a disease pandemic presents an important challenge for social marketing –to this point, health-related social marketing has focused on chronic diseases (such as cancer, asthma, obesity) and their risk factors (such as tobacco use, physical inactivity, and dietary intake). In the communicable disease field, most of the challenges we have addressed have had simple and proven preventive strategies (such as immunisation and the use of condoms). However, emerging pandemic diseases pose new challenges – notably in the global scale of the threat, the rapid nature of transmission, and (often) the absence of a known cure or vaccine. In this context, people’s quality of life has scope to be shaped by immense physical and social influences. This chapter reports on a comprehensive study undertaken to inform government policy and practice in the event of an avian influenza pandemic – specifically how to prepare (but not panic) the general public. The research phases included: a media analysis of coverage of a potential pandemic; extensive qualitative formative research; two population CATI surveys; two airport intercept surveys; message development; and message testing. While this research was undertaken in the context of a specific disease, the findings and recommendations are equally relevant to current and future pandemic threats.


Bacterial Biowarfare Agents


title: Theories of Biodiversity Value

text: The discussion of the calculus of biodiversity values in Chap. 5 is the final requisite prop for the stage across which this chapter parades accounts of how biodiversity is supposed to be valuable. The selection of these accounts is generous and represents a great majority of discussions on this topic, though it is not all-inclusive. It does include, among other theories, the theory that biodiversity is valuable for “unspecified moral reasons” (Sect. 6.1), that it is valuable as a resource (Sect. 6.2), as a service provider (Sect. 6.3), as a sustainer of human life (Sect. 6.4), as a key to human health, both as pharmacopoeia and as an inoculation against infection (Sect. 6.5), as the progenitor of human biophilic tendencies (Sect. 6.6), as a generator of (more) value (Sect. 6.7), as font of knowledge (Sect. 6.8), as having option (and quasi-option) value (Sect. 6.9), as transformative (Sect. 6.10), as having experiential value (Sect. 6.11), and as an expression of the natural order (Sect. 6.12). The chapter concludes (Sect. 6.13) with some proposals that are not customarily offered as self-contained theories of biodiversity value, but that are often suggested as still heavily influencing evaluation. These include what conservation biologists call “viability” and “endangerment” as well as conservation “efficiency”. Section 6.13 concludes with an extended discussion of the significance for biodiversity’s value of the history of human impingements on the natural world.


title: Pharmacogenomics and Molecular Diagnostics

text: To develop new Polymerase Chain Reaction (PCR)-based assays for nucleic acid detection for infectious diseases. Development of new assays on demand for emerging infectious diseases. For example, no proper nucleic acid-based tests exist for detection of H1N1 influenza virus. My lab, being the parasitology research unit aims to fill this gap by developing this ability.


title: Molecular Mechanisms of Flaviviral Membrane Fusion

text: Enveloped viruses rely on transmembrane fusion proteins to fuse the viral membrane to the host-cell membrane and deliver the viral genome into the cytoplasm for replication. Although the structures and evolutionary origins of viral fusion proteins vary widely, all fusion proteins use the same physical principles and topology to drive membrane fusion. First, exposure of a hydrophobic fusion anchor allows them to insert into the host-cell membrane. Conserved hydrophobic residues in the fusion anchor penetrate part way into the outer bilayer leaflet of the host-cell membrane. The fusion protein then folds back on itself, directing the C-terminal viral transmembrane anchor toward the fusion loop. This fold-back forces the host-cell membrane (held by the fusion loop) and the viral membrane (held by the C-terminal transmembrane anchor) against one another until they fuse. In West Nile virus and other flaviviruses this fold-back in the fusion protein, E, is triggered by the reduced pH of an endosome, is accompanied by the assembly of E monomers into trimers, and occurs by domain rearrangement rather than by an extensive refolding of secondary structure. The rearrangement releases a large amount of energy, which is used to exert a bending force on the apposed viral and cellular membranes, propelling them toward each other and, eventually, causing them to fuse. The conserved regions of E that are responsible for driving membrane fusion are attractive targets for antiviral therapies.


title: Traumatologie und gewaltsamer Tod

text: Vorgeschichte: Eine 39 Jahre alt gewordene, alkoholabhängige Frau habe von ihrem Hausarzt eine Packung Distraneurinkapseln (25 Stück) verschrieben bekommen; sie solle morgens und mittags je 1, abends 2 Kapseln einnehmen. Aus der Apotheke zurück gekehrt, begann sie zu Hause, mit ihrem Ehemann Alkohol zu trinken. Es sei zu einem Streit gekommen, in dessen Verlauf die Frau die Polizei angerufen habe. Der Ehemann sei daraufhin gegen 17.00 Uhr in Gewahrsam genommen und zur Wache verbracht worden. Ein Atemalkoholtest habe einen Atemalkoholwert von 1,29 mg/l ergeben. Gegen 04.00 Uhr morgens sei der Ehemann wieder entlassen worden (!). Er selbst habe angegeben, seine Ehefrau schlafend auf dem Sofa angetroffen zu haben; er habe sie geweckt, sie habe u.a. zu ihm gesagt, dass sie die Distraneurintabletten eingenommen habe. Ihr Zustand habe sich deutlich von dem bei sonstiger Alkoholisierung unterschieden. Gegen 05.30 Uhr habe er den Notarzt verständigt, der nur noch den Tod feststellen konnte.


title: Infectious Diseases: The Role of the Forensic Physician

text: Infections have plagued doctors for centuries, in both the diagnosis of the specific diseases and the identification and subsequent management of the causative agents. There is a constant need for information as new organisms emerge, existing ones develop resistance to current drugs or vaccines, and changes in epidemiology and prevalence occur. In the 21st century, obtaining this information has never been more important. Population migration and the relatively low cost of flying means that unfamiliar infectious diseases may be brought into industrialized countries. An example of this was an outbreak of severe acute respiratory syndrome (SARS), which was first recognized in 2003. Despite modern technology and a huge input of money, it took months for the agent to be identified, a diagnostic test to be produced, and a strategy for disease reporting and isolation to be established. There is no doubt that other new and fascinating diseases will continue to emerge.


title: (13)C Chemical Shifts in Proteins: A Rich Source of Encoded Structural Information

text: Despite the formidable progress in Nuclear Magnetic Resonance (NMR) spectroscopy, quality assessment of NMR-derived structures remains as an important problem. Thus, validation of protein structures is essential for the spectroscopists, since it could enable them to detect structural flaws and potentially guide their efforts in further refinement. Moreover, availability of accurate and efficient validation tools would help molecular biologists and computational chemists to evaluate quality of available experimental structures and to select a protein model which is the most suitable for a given scientific problem. The (13)C(α) nuclei are ubiquitous in proteins, moreover, their shieldings are easily obtainable from NMR experiments and represent a rich source of encoded structural information that makes (13)C(α) chemical shifts an attractive candidate for use in computational methods aimed at determination and validation of protein structures. In this chapter, the basis of a novel methodology of computing, at the quantum chemical level of theory, the (13)C(α) shielding for the amino acid residues in proteins is described. We also identify and examine the main factors affecting the (13)C(α)-shielding computation. Finally, we illustrate how the information encoded in the (13)C chemical shifts can be used for a number of applications, viz., from protein structure prediction of both α-helical and β-sheet conformations, to determination of the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH or to accurate detection of structural flaws, at a residue-level, in NMR-determined protein models.


title: Era of Intelligent Systems in Healthcare

text: The aim of this chapter is to prepare the reader for the outstanding trip that she/he embarked when starting reading this book. At first, we shall try to look for answers to some of the most important questions regarding the connection between intelligent systems and healthcare. What are intelligent systems? How can they be used in healthcare? Have they got benefits and prospects? Let us highlight some of the decisive factors for a successful deployment of intelligent systems in healthcare, including intelligent clinical support and intelligent patient management.


title: Behavioral Epidemiology of Infectious Diseases: An Overview

text: The focus of the growing discipline of behavioral epidemiology (BE) of infectious diseases is on individual behavior as a key determinant of infection trajectories. This overview departs from the central, but static, role of human behavior in traditional mathematical models of infection to motivate the importance of including behavior into epidemiological models. Our aim is threefold. First, we attempt to motivate the historical and cultural background underpinning the BE revolution, focusing on the issue of rational opposition to vaccines as a natural endpoint of the changed relation between man and disease in modern industrialized countries. Second, we review those contributions, from both mathematical epidemiology and economics, that forerun the current “epidemic” of studies on BE. Last, we offer a more detailed overview of the current epidemic phase of BE studies and, still motivated by the issue of immunization choices, introduce some baseline ideas and models.


Market Trends in Lateral Flow Immunoassays


title: Quantitative Performance Monitoring of China’s HIV Response

text: China has made tremendous progress in advancing its national HIV program. Key to this progress was setting targets to motivate implementers to work effectively. Indicators were established using an iterative process with national stakeholders while also meeting international pressures. A plethora of demands may have distracted from ownership of the initial national program but, in the end, strengthened a focus on marginalized groups. China gradually relied less on donors and developed a uniquely Chinese HIV control program. The result was remarkable enlargement of prevention and treatment services that led to a reduction in mortality. Setting targets, and measuring performance against those targets, was vital to gauge continued progress and identify gaps in programing and implementation.


title: Grundlagen der systemischen Therapie

text: Die Möglichkeiten einer systemischen Therapie maligner Erkrankungen - außerhalb der zytostatischen Chemotherapie - sind in den letzten Jahren deutlich erweitert worden. Dazu haben insbesondere neue Erkenntnisse zur molekularen Pathogenese von Tumorerkrankungen beigetragen. Von besonderem Interesse sind Strategien, die in Prozesse der tumorassoziierten Neoangiogenese oder der neoplastischen Wachstumsregulation eingreifen.


title: Bronchite acuta

text: La bronchite acuta è una infiammazione dei bronchi primari e secondari ed è una delle patologie relativamente più frequenti nella pratica clinica, anche se la sua definizione rimane, per certi aspetti, non sempre ben definita. La localizzazione del processo infiammatorio spesso coinvolge tratti respiratori limitrofi (faringe, laringe, trachea, bronchi, bronchioli) determinando un interessamento progressivo dell’albero bronchiale.


title: Nanomolecular Diagnostics

text: Clinical application of molecular technologies to elucidate, diagnose and monitor human diseases is referred to as molecular diagnosis. It is a broader term than DNA (deoxyribonucleic acid) diagnostics and refers to the use of technologies that use DNA, RNA (ribonucleic acid), genes or proteins as bases for diagnostic tests. The scope of the subject is much wider and includes in vivo imaging and diagnosis at single molecule level. A more detailed description of molecular diagnostics is presented elsewhere (Jain 2017a).


title: Nanotechnological Approaches for Genetic Immunization

text: Genetic immunization is one of the important findings that provide multifaceted immunological response against infectious diseases. With the advent of r-DNA technology, it is possible to construct vector with immunologically active genes against specific pathogens. Nevertheless, site-specific delivery of constructed genetic material is an important contributory factor for eliciting specific cellular and humoral immune response. Nanotechnology has demonstrated immense potential for the site-specific delivery of biomolecules. Several polymeric and lipidic nanocarriers have been utilized for the delivery of genetic materials. These systems seem to have better compatibility, low toxicity, economical and capable to delivering biomolecules to intracellular site for the better expression of desired antigens. Further, surface engineering of nanocarriers and targeting approaches have an ability to offer better presentation of antigenic material to immunological cells. This chapter gives an overview of existing and emerging nanotechnological approaches for the delivery of genetic materials.


title: The Successes and Failures of Global Health Organizations: The World Health Organization, UNAIDS, Médicins sans Frontières and PEPFAR

text: Chapter 7 examined the operations of multilateral, bilateral and private donors in financing the fight against HIV/AIDS. This chapter examines the operations of five organizations that focus more directly on addressing HIV/AIDS health issues on the ground: the World Health Organization; UNAIDS; Médicins sans Frontières (Doctors without Borders); the US President’s Emergency Plan for AIDS Relief (PEPFAR); and the US Centers for Disease Control and Prevention. The first two form part of the United Nations (UN) system, the third is a private, non-profit non-governmental organization that relies on volunteers to deliver medical services and products in developing countries that are facing health crises and the fourth and fifth are a US government program and agency, respectively. The UN has won the Nobel Peace Prize a number of times: UN Middle East mediator (1950); UNHCR, the UN refugee agency (1954); UN Secretary-General (1961); UNICEF (1965); ILO, the UN labor agency (1969); UNHCR, the UN refugee agency (1981); UN peacekeeping (1988); and UN Secretary-General and the UN, jointly (2001). There are several bodies inside the UN that also have won the Nobel Peace Prize, such as the International Atomic Energy Agency (2005) and Director Mohamed El-Baradei and the Intergovernmental Panel on Climate Change (2007). In addition, the prime minister of Canada, Lester Bowles Pearson, won Nobel Peace Prize for his work with the UN (1957). Médicins sans Frontières has won the Nobel Peace Prize once (1999)


title: The Impact of Disease on Welfare

text: Welfare is usually defined in terms either of an animal’s ability to cope (Broom, 1986) or of health and behavioural needs. Indeed the very word “dis-ease” implies a state lacking “ease” or well-being. We feel it is important to consider disease holistically: that is to consider the animal’s ability to resist stress and the environmental challenges it faces. Whereas the outcome of poor welfare is expressed as disease, the relative contributions of various stressors will vary with each individual. The other chapters consider genetics, nutrition and environment in terms of the welfare of poultry. However, given the same housing, air, feed and water, some birds may become diseased and some remain healthy. Intrinsic biological variation results in a range of nutrient reserves and immune status at hatching, plus differences in genetic make up, social status and behaviour that interact with each other and further factors to provide different outcomes for the individual. In the pragmatic world of farming, flock health status may be frequently chosen as the index of welfare, but it is important not to lose sight of the health and well-being of each individual, even in flocks numbering tens of thousands of birds.


Myzetom


title: How Does Biodiversity Influence the Ecology of Infectious Disease?

text: Over the past years, biodiversity has been reduced on an unprecedented scale, while new infectious diseases are emerging at an increasing rate. Greater overall biodiversity could lead to a greater diversity of hosts and thus of pathogens. Yet disease regulation – due to the buffering role of host diversity – is considered to be one of the services provided by biodiversity. In this chapter, we ask how biodiversity is linked to infectious disease. First, we investigate the influence of the biodiversity of pathogens. We highlight that the number of pathogen species is not well known but that new findings are facilitated by the rapid expansion of molecular techniques. We show that, although there is a trend to find higher pathogen richness toward the equator, identifying a global pattern between the richness of all pathogen species and their latitudinal distribution is challenging. We emphasize that pathogen intraspecific diversity is a crucial factor in disease emergence and allows pathogens to adapt to the selective pressures they face. In addition, the selective pressure acting on hosts due to parasite, and reinforced by parasite diversity within hosts seems to be a major evolutionary and ecological force shaping hosts biodiversity. Second, we investigate how the diversity of hosts influences infectious disease ecology. For multi-host diseases, a change in host species richness or abundance can modify the dynamics of local infectious diseases by either reducing (“dilution effect”) or increasing (“amplification effect”) the risk of transmission to the targeted host species. The underlying hypothesis is that, the competence of reservoirs varies according to the host species. The dilution effect has been demonstrated mainly through theoretical work and there have been only few case studies. Regarding the genetic diversity of host, an important issue is: to what extent does a reduction of this diversity impact the ability of the host population to response to infectious diseases? Third, we rapidly examine the role of biodiversity in the treatment of infectious diseases. To conclude, we consider that the consequences of the loss of species biodiversity on infectious diseases is still largely unknown, notably due to the lack of knowledge on the dynamics of host-pathogen relationships, especially at the population and at the community level.. We highlight that work on multi-host/ ulti-pathogen systems should be fostered and that new approaches, such as metagenomic investigations that does not require a priori assumptions, are promising to describe a community of pathogens and their interactions.


title: Performing Interventions: The Politics and Theatre of China’s AIDS Crisis in the Early Twenty-First Century

text: Theatrical productions attest to a radical shift in Chinese governmental policy and public awareness of the AIDS epidemic at the dawn of the twenty-first century; state-subsidised theatre worked directly with the government to contain the transmission of HIV. Produced by two of the country’s most elite cultural institutions, the Shanghai Dramatic Arts Center and the Beijing People’s Art Theatre respectively, The Dying Kiss (Shengsi Zhiwen) in 2003 and Student Zhao Ping (Zhao Ping Tongxue) in 2005 represented a sea change in the political response to the epidemic while documenting public perceptions towards people living with HIV and AIDS in China. Marking policy change, they reflect experiences that capture a society transitioning from denial to confrontation at the dawn of the twenty-first century.


title: The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics

text: The Ubiquitin-Proteasome System (UPS) plays an important role in the setting of the cellular response to multiple stress signals. Although the primary function of ubiquitin was initially associated with proteolysis, it is now considered as a key regulator of protein function controlling, among other functions, signalling cascades, transcription, apoptosis or oncogenesis. Failure at any level of the UPS is associated with the development of multiple pathologies including metabolic problems, immune diseases, inflammation and cancer. The successful use of the proteasome inhibitor Bortezomib (Velcade) in the treatment of multiple myeloma (MM) and mantle cell lymphoma (MCL) revealed the potential of the UPS as pharmacological target. Ten years later, new inhibitors tackling not only the proteasome but also different subsets of enzymes which conjugate or de-conjugate ubiquitin or ubiquitin-like molecules, have been developed. Most of them are excellent tools to characterize better the emerging molecular mechanisms regulating distinct critical cellular processes. Some of them have been launched already while many others are still in pre-clinical development. This chapter updates some of the most successful efforts to develop and characterize inhibitors of the UPS which tackle mechanisms involved in cancer. Particular attention has been dedicated to updating the status of the clinical trials of these inhibitors.


Disruptive Behaviors: Should We Foster or Prevent Resiliency?


title: Emerging Issues in Environmental and Occupational Lung Diseases

text: Humans continue to introduce new or greatly modified agents and techniques into the workplace and environment. These new agents and altered practices lead to evolving patterns of established diseases as well as entirely novel conditions never experienced before in medical history. Although many of these emerging conditions appear in the literature as case reports or case series, these sentinel cases frequently raise the public awareness that drives social movements or, in some situations, represent a warning sign for subsequent outbreaks. The emerging environmental and occupational lung diseases (EOLD) may be grouped arbitrarily into two categories: (1) conditions caused by novel utilization or routes of exposure to agents known to cause EOLD and (2) conditions caused by novel agents not known to cause specific EOLD in the past. Conditions in the first category may include those caused by new exposure scenarios in nonindustrial settings and thus a large population may be at risk. The second category includes new risk factor(s) that were not known to be associated with a specific EOLD, and thus the association between the agent and the new condition could be easily missed. Clinicians should remain astute and vigilant when evaluating the potential role of environmental risk factors in any lung diseases and especially pay attention to the identification of clusters of cases of disease of unknown etiology.


title: Sexual Dysfunction

text: Female sexual dysfunction or dissatisfaction is a common complaint among obstetric-gynecology patients. These complaints may result from medical treatments and procedures, or may secondarily complicate the management and patient compliance of treatment for other medical issues. Therefore, it is important that clinicians treating females obtain basic information regarding human sexual function and dysfunction. This chapter presents an integration of the clinical research as well as the author’s experience regarding sexual function and the management of sexual problems often presented in an obstetricgynecology practice.


Common Colds and Respiratory Viruses: Impact on Allergy and Asthma


title: Acute Respiratory Failure After Hematopoietic Stem Cell Transplantation

text: Infectious and noninfectious pulmonary complications are common among HSCT recipients and are the leading cause for respiratory failure requiring mechanical ventilation and ICU admission. Unique pulmonary syndromes include peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, and idiopathic pneumonia syndrome. Respiratory failure requiring mechanical ventilation after HSCT continues to be associated with a poor prognosis.


title: Engineering Control of Airborne Disease Transmission in Health Care Facilities

text: Hospital acquired illness or “nosocomial” illness is of increasing concern to public health administrators, hospitals, physicians and patients. Engineering infection control measures are used to reduce the concentration and prevent the spread of these particles throughout a building in order to decrease exposure to and risk of illness from infectious pathogens. The engineer who attempts to deal with microbial indoor air quality finds that pertinent microbiological information exists in abundance but not in easily digestible forms. This paper will provide a brief review of the problem of controlling airborne disease transmission in healthcare facilities with emphasis on medical microbiology and aerobiology in order to offer some conclusions regarding the potential for engineering control of infectious diseases.


title: Nutrition and the Gastrointestinal System

text: The following chapter will focus on the gastrointestinal system and nutrition. Pertinent questions, answers, and rationale will be reviewed. Answers for this chapter can be found beginning on page 136.


title: Expert-Based Scenarios for the Logistics Service Industry 2025

text: The previous chapter 7 represented the first research part of this thesis. It captured the current state of scenario planning practices in the logistics service industry from an internal and an external perspective. It revealed, in line with the literature review, a backward picture of such planning practices compared to industry sector standard and overall. The need for an exemplary industry focused scenario study in the logistics environment was particularly worked out in the chapters 5.3 (literature review) and 7.3 (conclusion of triangulation research). This chapter 8 presents the research results of research phase II and therefore addresses the identified research gap.


title: Department of Defense Global Emerging Infections System Programs in Biodefense

text: One of the great fallacies of the mid-20th century was that infectious diseases were nearing elimination. In the face of those prognostications, more than 25 new infectious diseases were recognized for the first time between 1975 and 2000. These new scourges included HIV, Ebola, Legionnaire’s Disease, Hantavirus pulmonary syndrome, deadly new strains of influenza, and new forms of drug-resistant bacteria and malaria. Rather than nearing extinction as a broad class of human suffering, infectious diseases remain the leading cause of death worldwide. The ability of microbes to adapt to new pressures, including antibiotic usage coupled with changes in society, technology, and the environment make it likely that the microbial threat will remain a threat to humanity, and even suggests the possibility of regional and global epidemics comparable to the worst in history.


title: Nanomaterials-Based siRNA Delivery: Routes of Administration, Hurdles and Role of Nanocarriers

text: Ribonucleic acid interference (RNAi) is a potential alternative therapeutic approach to knock down the overexpression of genes in several disorders especially cancers with underlying genetic dysfunctions. For silencing of specific genes involved in cell cycle, small/short interfering ribonucleic acids (siRNAs) are being used clinically. The siRNA-based RNAi is more efficient, specific and safe antisense technology than other RNAi approaches. The route of siRNA administration for siRNA therapy depends on the targeted site. However, certain hurdles like poor stability of siRNA, saturation, off-target effect, immunogenicity, anatomical barriers and non-targeted delivery restrict the successful siRNA therapy. Thus, advancement of an effective, secure, and long-term delivery system is prerequisite to the medical utilization of siRNA. Polycationic nanocarriers mediated targeted delivery system is an ideal system to remove these hurdles and to increase the blood retention time and rate of intracellular permeability. In this chapter, we will mainly discuss the different biocompatible, biodegradable, non-toxic (organic, inorganic and hybrid) nanocarriers that encapsulate and shield the siRNA from the different harsh environment and provides the increased systemic siRNA delivery.


title: Detection of Viral RNA Splicing in Diagnostic Virology

text: This chapter is the first one to introduce the detection of viral RNA splicing as a new tool for clinical diagnosis of virus infections. These include various infections caused by influenza viruses, human immunodeficiency viruses (HIV), human T-cell leukemia viruses (HTLV), Torque teno viruses (TTV), parvoviruses, adenoviruses, hepatitis B virus, polyomaviruses, herpesviruses, and papillomaviruses. Detection of viral RNA splicing for active viral gene expression in a clinical sample is a nucleic acid-based detection. The interpretation of the detected viral RNA splicing results is straightforward without concern for carry-over DNA contamination, because the spliced RNA is smaller than its corresponding DNA template. Although many methods can be used, a simple method to detect viral RNA splicing is reverse transcription-polymerase chain reaction (RT-PCR). In principle, the detection of spliced RNA transcripts by RT-PCR depends on amplicon selection and primer design. The most common approach is the amplification over the intron regions by a set of primers in flanking exons. A larger product than the predicted size of smaller, spliced RNA is in general an unspliced RNA or contaminating viral genomic DNA. A spliced mRNA always gives a smaller RT-PCR product than its unspliced RNA due to removal of intron sequences by RNA splicing. The contaminating viral DNA can be determined by a minus RT amplification (PCR). Alternatively, specific amplification of a spliced RNA can be obtained by using an exon-exon junction primer because the sequence at exon-exon junction is not present in the unspliced RNA nor in viral genomic DNA.


Microfluidic Diagnostic Systems for the Rapid Detection and Quantification of Pathogens


title: Il lavaggio broncoalveolare nelle pneumopatie infiltrative diffuse

text: Le pneumopatie infiltrative diffuse costituiscono un gruppo eterogeneo di malattie caratterizzate, istologicamente, dalla presenza di un danno a carico della parete alveolare che puÒ essere infiltrata da cellule infiammatorie/neoplastiche/fluidi/tessuto connettivo. Si parla di forme “diffuse” per sottolineare l’interessamento non solo dell’interstizio, ma anche delle strutture acinari e bronchiolari.


title: Global Issues and Health Interactions: Reflexions from the South

text: This chapter draws attention to a range of global issues that interact, and aims to provoke thought and research on their impact on health. Initially, it deals with communication, economic issues and physician migration. Then it summarizes a wide field of mechanisms by which global forces affect health, indirectly or directly. Within this classification there has to be some overlap—for example the HIV virus causing AIDS would appear to be a direct health effect, but a shift in lifestyles that has seen an increase in the number of individuals’ sexual partners—a shift that perhaps reflects a breakdown of family and religious value systems—may be the more fundamental, but indirect, cause. The view is primarily from the standpoint of developing countries, the “South,” and does not eschew controversy.


title: Investigating Protein Adsorption via Spectroscopic Ellipsometry

text: In this chapter, the basic concepts behind ellipsometry and spectroscopic ellipsometry are discussed along with some instrument details. Ellipsometry is an optical technique that measures changes in the reflectance and phase difference between the parallel (R (P)) and perpendicular (R (S)) components of a polarized light beam upon reflection from a surface. Aside from providing a simple, sensitive, and nondestructive way to analyze thin films, ellipsometry allows dynamic studies of film growth (thickness and optical constants) with a time resolution that is relevant to biomedical research. The present chapter intends to introduce ellipsometry as an emerging but highly promising technique, that is useful to elucidate the interactions of proteins with solid surfaces. In this regard, particular emphasis is placed on experimental details related to the development of biomedically relevant conjugated surfaces. Results from our group related to adsorption of proteins to nanostructured materials, as well as results published by other research groups, are discussed to illustrate the advantages and limitations of the technique.


title: Biologics

text: Currently, ~28–30 mAbs are approved or under consideration for approval as specific therapies in the USA or European Union, although about 350 new mAbs for therapeutic application in humans are in the commercial pipeline. So far, the number of target antigens for the mAbs is surprisingly small with more than one of the approved antibodies specific for TNF, HER2, CD20, EGFR, or VEGF. Other specificities include EpCAM, glycoprotein IIb/IIIa, CD30, CD52, C5, α-4 integrin, IgE, IL-6R, BLys, IL-1β, and RANK-L. Initial infusion reactions to some mAbs may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Systemic and cutaneous reactions also occur to mAbs. Rituximab, for example, may cause serum sickness, vasculitis, cutaneous reactions, interstitial pneumonitis, and ARDS as well as post-infusion reactions. Some patients receiving cetuximab experienced severe immediate hypersensitivity reactions. The antibodies involved are IgE specific for α-d-galactose-(1–3)-β-d-galactose and reactive with this disaccharide present on the Fab portion of the chimeric antibody. The nature of, and main adverse reactions to, etanercept, the synthetic IFNs pegylated IFNα-2a and pegylated IFNα-2b, IL-2, denileukin diftitox, anakinra, aflibercept, anti-thymocyte globulin, epoetins, and recombinant human insulin are discussed.


title: Recent Experiences in Parameter-Free Data Mining

text: Recent results supporting the usefulness of the normalized compression distance for the task to classify genome sequences of virus data are reported. Specifically, the problem to cluster the hemagglutinin (HA) sequences of in uenza virus data for the HA gene in dependence on the host and subtype of the virus, and the classification of dengue virus genome data with respect to their four serotypes are studied. A comparison is made with respect to hierarchical and spectral clustering via the kLine algorithm by Fischer and Poland (2004), respectively, and with respect to the standard compressors bzlip, ppmd, and zlib. Our results are very promising and show that one can obtain an (almost) perfect clustering for all the problems studied.


title: Flu or a Bug?

text: Of late, apart from the four calendar seasons, there is yet another season referred to as the “flu season.” During this time of the year, we routinely hear the phrase “the flu is going around.” I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word “bug” is used so callously by adults that it has been registered wrongly in the minds of the little ones.


title: Virology

text: Molecular techniques have become indispensable in viral diagnostics. Current applications include: (1) The detection of (unknown) viral infections in clinical samples. (2) Quantitative monitoring of viral load. (3) Genotyping of viral strains. (4) Detection of mutations in the viral genome that are associated with viral resistance. Proper sample acquisition and sample transport, as well as accurate DNA or RNA isolation are a prerequisite for reliable test results in molecular diagnostics of viral infections. In-house as well as commercial assays can be used for the amplification of viral DNA or RNA for the detection of viral infections and viral load monitoring. Many virus species consist of several subspecies, genotypes or variants. This molecular variation has to be taken into account when applying molecular diagnostics. More complicated diagnostics for genotyping or the detection of mutations related to therapy failure often rely on sequencing, although for some viral targets commercial assays are available. In this chapter, applications are described in which molecular methods have become the most important form of viral diagnostics. Molecular test results have a direct impact on patient management and as such, results have to be reliable, standardized and reproducible. Therefore, quality control and standardization are important issues!


title: Great Plagues of the Past and Remaining Questions

text: Due to the difficulty of obtaining tissue samples from victims of the ancient plagues, it is not always possible to utilise palaeomicrobiology techniques to determine the etiology of ancient infection. Therefore, it is often necessary to utilise other means to arrive at a likely diagnosis. The most helpful of these is the literary description of the disease. While this is often the best evidence available, working with such documents can prove difficult. Three great plagues of the ancient world, the Plague of Athens, the Antonine Plague, and the Justiniac Plague are described in either Latin or ancient Greek. The difficulties encountered when translating any ancient foreign language are compounded by the fact that so many words in these languages have a variety of meanings. This chapter reviews the three great plagues of antiquity from a clinical perspective.


title: Multiplex PCR in Molecular Differential Diagnosis of Microbial Infections: Methods, Utility, and Platforms

text: We are entering the age of personalized medicine where treatments are designed to target specific causes, rather than a group of patients with similar symptoms. However, personalized medicine is impossible without a personalized diagnosis that considers all the possible causes of a person’s disease. Traditional molecular diagnostic methods, such as PCR and qPCR, cannot provide the necessary information to practice personalized medicine, because they cannot be multiplexed, allowing the detection of only one or a few (no more than 3) targets at a time in one sample. Practicing personalized medicine, therefore, requires multiplex PCR (mPCR), which can evaluate many molecular targets at once, in one reaction, from one sample.


title: Physiologie und Pathophysiologie der Zelle

text: Die Kenntnis des Aufbaues einer Zelle ist wichtig, um biochemischen Veränderungen funktionelle Störungen auf zellulärem Niveau zuordnen zu können (Bruce et al., 2004). Von Bedeutung sind die Membranen, deren Funktionen im Wesentlichen durch Membranproteine vermittelt werden, die intrazellulären Organellen als Räume spezifischer Reaktionen und das Zytoskelett, welches Stabilität, Motilität und den intrazellulären Transport von zellulären Strukturen und Vesikeln ermöglicht.


title: Cardiovascular Anatomy and Pharmacology

text: This chapter reviews the cardiovascular anatomy, the effects of medications on the cardiovascular system, and current guidelines. Patients in the perioperative period often receive agents that affect hemodynamic variables such as heart rhythm and rate, blood pressure, or cardiac output.


title: Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery

text: A key requirement for topical and transdermal active delivery is the effective delivery of an active to a desired target site, to achieve both safe and efficacious outcomes. This chapter seeks to explore the importance of the pharmacological, toxicological and therapeutic properties of actives and excipients, as well as the site of action as complementary components in percutaneous absorption. This is crucial for optimized topical and transdermal product design.


title: Noninvasive Mechanical Ventilation: Models to Assess Air and Particle Dispersion

text: Respiratory failure is a major complication of viral infections such as severe acute respiratory syndrome (SARS) [1], avian influenza H5N1 infection [2], and the 2009 pandemic influenza (H1N1) infection [3]. The course may progress rapidly to acute respiratory distress syndrome (ARDS) and multi-organ failure, requiring intensive care. Noninvasive ventilation (NIV) may play a supportive role in patients with severe viral pneumonia and early ARDS/acute lung injury. It can act as a bridge to invasive mechanical ventilation, although it is contraindicated in critically ill patients with hemodynamic instability and multi-organ dysfunction syndrome [4]. Transmission of some of these viral infections can convert from droplets to airborne during respiratory therapy.


title: Bioinformatics and Translation Elongation

text: Codon usage depends on mutation bias, tRNA-mediated selection, and the need for high efficiency and accuracy in translation. One codon in a synonymous codon family is often strongly over-used, especially in highly expressed genes, which often leads to a high dN/dS ratio because dS is very small. Many different codon usage indices have been proposed to measure codon usage and codon adaptation. Sense codon could be misread by release factors and stop codons misread by tRNAs, which also contribute to codon usage in rare cases. This chapter outlines the conceptual framework on codon evolution, illustrates codon-specific and gene-specific codon usage indices, and presents their applications. A new index for codon adaptation that accounts for background mutation bias (Index of Translation Elongation) is presented and contrasted with codon adaptation index (CAI) which does not consider background mutation bias. They are used to re-analyze data from a recent paper claiming that translation elongation efficiency matters little in protein production. The reanalysis disproves the claim.


title: Viren mit einzelsträngigem, segmentierten RNA-Genom in Negativstrangorientierung

text: Bis heute sind drei Virusfamilien bekannt, deren Vertreter ein RNA-Genom mit negativer Orientierung besitzen, das in den infektiösen Viruspartikeln nicht als ein kontinuierliches Molekül, sondern in mehreren Segmenten vorliegt. Es handelt sich um die Arenaviridae, die Bunyaviridae und die Orthomyxoviridae. Ähnlich wie die Mononegavirales (▸ Kapitel 15) benötigen auch sie für die Synthese der mRNA und für die Replikation ein spezielles Enzym, das zusammen mit weiteren Virus-komponenten bei der Infektion in die Zelle gelangt: die RNA-abhängige RNA-Polymerase. Ein in Segmenten vorliegendes Genom ermöglicht den Viren die Bildung von Reassortanten. Hier werden die RNA-Moleküle bei Doppelinfektionen von Zellen mit unterschiedlichen Virus-typen während der Replikation und der Morphogenese gemischt. Die Nachkommenviren können so Neukombinationen der RNA-Segmente und damit neue Eigenschaften erhalten. Besonders häufig und gut untersucht ist dieser Mechanismus, der als antigenic shift bezeichnet wird, bei den Influenza-A-Viren, den Erregern der Virus-influenza oder echten Grippe (▸ Abschnitt 16.3).


title: Detection of Bovine Coronavirus by Conventional Reverse Transcription Polymerase Chain Reaction

text: Bovine coronavirus (BCoV) is an economically significant cause of enteric and respiratory diseases in cattle throughout the world. BCoV is a known cause of neonatal calf diarrhea, winter dysentery in adult cattle, and respiratory disorders in cattle of all ages. In this chapter, we describe a simple and efficient protocol for total nucleic acids extraction to be used in conventional RT-PCR assay. This is a technique used routinely in our virology laboratory to detect BCoV from stool and nasopharyngeal samples of cattle.


title: Drug Development Research

text: Infectious diseases are significant causes of human mortality, morbidity, and economic loss. Although effective antimicrobial agents are available for treating bacterial infections, as are limited agents for viral, fungal, and parasitic infections, many diseases are still very difficult to treat effectively and may present serious health concerns. The emergence of drug resistance among common pathogens continues to render ineffective many previously frontline therapies, and the use of many drugs is often limited by toxicity concerns. Emergence of diseases caused by new or drug-resistant pathogens demands more effective drugs. However, current advances in chemistry, bioinformatics, and structural biology should make it possible to discover or design novel anti-infective agents that target specific functions required for pathogen growth and pathogenesis (http://www3.niaid.nih.gov/about/organization/dmid/overview.htm).


title: Mitochondria and Antiviral Immunity

text: Mitochondria are unique dynamic organelles that evolved from free-living bacteria into endosymbionts of mammalian hosts (Sagan 1967; Hatefi 1985). They have a distinct ~16.6 kb closed circular DNA genome coding for 13 polypeptides (Taanman 1999). In addition, a majority of the ~1500 mitochondrial proteins are encoded in the nucleus and transported to the mitochondria (Bonawitz et al. 2006). Mitochondria have two membranes: an outer smooth membrane and a highly folded inner membrane called cristae, which encompasses the matrix that houses the enzymes of the tricarboxylic acid (TCA) cycle and lipid metabolism. The inner mitochondrial membrane houses the protein complexes comprising the electron transport chain (ETC) (Hatefi 1985).


title: Advocating Global Health Security

text: For the last two decades, a recurring strategy employed by health professionals, scientists, and diplomats has been to play the ‘health security card’ to achieve particular trade, diplomatic, strategic, and development goals. The presumption has been that the securitisation of health will harness global political leadership and resources. This marriage of health issues to security logic has been met with a mix of applause, caution, and critique. In particular, there have been growing claims that the successful global health initiatives such as, the Global Fund for AIDS, TB, and Malaria (Global Fund) and the Global Alliance for Vaccine Immunization (GAVI) were achieved without asserting their necessity on security considerations. Thus, what difference does the association of security to health make for the success and longevity of global health initiatives? In this chapter, I answer this question through comparing a case where the security logic was deliberately deployed to frame the ‘health emergency’ (Framework Convention on Tobacco Control), against a case where human rights logic was used to advocate for its creation (the GAVI). I critically explore the conditions under which linking securitisation with an international health initiative captures and maintains political leadership and resources.


title: DNA, RNA und IHRE Amplifikation

text: DNA heißt die magische Helix des Lebens — der materielle Träger der Erbsubstanz, die Desoxyribonucleinsäure (DNA, deoxyribonucleic acid) (siehe Box 6.1).


title: Alcohol and HIV: Experimental and Clinical Evidence of Combined Impact on the Lung

text: Despite antiretroviral therapy, lung disease is a leading cause of death in individuals infected with human immunodeficiency virus type 1 (HIV). Individuals infected with HIV are susceptible to serious bacterial and viral infections, such as pneumococcus and influenza, which are particularly problematic for lung health, resulting in lung injury. Additionally, HIV-infected individuals are susceptible to a number of pulmonary diseases for unknown reasons. Alcohol, the most commonly abused drug in the world, continues to exact an enormous toll on morbidity and mortality in individuals living with HIV. Chronic alcohol abuse has been shown to affect lung immunity, resulting in significant lung injury. There is a paucity of literature on the additive effects of HIV and alcohol, two diseases of immune senescence, in the lung. This chapter begins by discussing the latest literature evaluating the epidemiology of HIV, alcohol use, and lung health focusing on two prevalent infections, tuberculosis and pneumococcal pneumonia. In parallel, we discuss the interactions of alcohol and HIV on the risk for acute lung injury and subsequent morbidity and mortality. We then discuss the pathophysiology of how these two diseases of immune dysfunction affect the lung, with a focus on the oxidative stress, alveolar macrophage host immune capacity, and immunomodulatory role of zinc in the airway. Finally, we review the latest literature on how HIV and alcohol affect other pulmonary disorders including chronic obstructive pulmonary disease, pulmonary hypertension, and lung cancer.


Schlafkrankheitserreger


title: Gastroenteric Viruses

text: In recent years, viruses have been recognized increasingly as an important cause of foodborne infections. More than 160 enteric viruses are excreted in the feces of infected individuals, and some may also be present in the vomitus. Food and water are directly contaminated with fecal material, through the use of sewage sludge in agriculture, sewage pollution of shellfish culture beds, or may be contaminated by infected food-handlers.


title: The Discovery Process of SFTS in China

text: Heightened surveillance of acute febrile illness in China since 2004 led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with unknown etiology. Sporadic patients hospitalized with SFTS in 2009 and 2010 were identified and serum samples were collected. Sequence from a novel species of phlebovirus was identified by sequence independent single primer amplification (SISPA) from the serum of a patient with SFTS. The virus was isolated in Vero cell culture and its complete genome sequence was determined, only distantly related to other known phleboviruses. Electron microscopic analysis revealed a virion morphologically characteristic of phleboviruses. The virus was named as SFTS virus. The viral RNA and/or specific antibodies were detected from the blood of patients with SFTS. Serological assays demonstrated a virus-specific immune response in pairs of sera collected from patients at acute and convalescent phases. The pathogenic mechanisms of thrombocytopenia in human SFTS disease was resembled in a mouse model. The results had been collected to demonstrate that SFTS virus was etiologically associated with an acute and novel infectious disease, SFTS in humans.


title: Social Network Analysis for Contact Tracing

text: Contact tracing is an important control measure in the fight against infectious disease. Healthcare workers deduce potential disease pathways and propose corresponding containment strategies from collecting and reviewing patients’ contact history. Social Network Analysis (SNA) provides healthcare workers with a network approach for integrating and analyzing all collected contact records via a simple network graph, called a contact network. Through SNA, they are able to identify prominent individuals in disease pathways as well as study the dynamics of disease transmission. In this chapter, we review the role of SNA in supplementing contact tracing and present a case study of the Taiwan SARS outbreak in 2003 to demonstrate the usefulness of geographical contacts to disease investigation.


title: Acute and chronic liver insufficiency

text: The term “liver insufficiency” denotes a break down in the functions of the liver. The syndrome of functional liver failure covers a wide spectrum of clinical, biochemical and neurophysiological changes. In principle, liver insufficiency can occur without previous liver damage as well as with already existing liver disease. It is characterized by a deterioration in the synthesizing, regulatory and detoxifying function of the liver. This final stage of liver disease terminates in hepatic coma.


title: Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

text: Erythema multiforme in its most extreme form has traditionally been divided between toxic epidermal necrolysis and Stevens-Johnson Syndrome. These two life-threatening skin diseases are now considered part of the same spectrum of disease. They can be differentiated by clinical and histological criteria. We can also now predict which patients are apt to have the most guarded prognosis. Treatment by multiple agents is imperfect, but offers a better chance of a good outcome than ever before.


title: Computational Vaccinology

text: In this chapter we shall review recent developments in computational vaccinology, highlighting work in the area of epitope and antigen identification, and the discovery of delivery vectors and adjuvants. These diverse activities all have the potential to reduce significantly the laboratory resource needed for efficient vaccine discovery. We discuss how computational analysis of pathogenic genomes by epitope mapping and reverse vaccinology can provide viable vaccine targets.


title: Primordial and Primary Levels of Biothreat and Bioterrorism Prevention

text: There is still an abundance of preventive and solving measures against biological attacks that makes confusion and dezorientation among experts and health policy-makers. Our pyramidal model of adversaries, and spherical system of prevention help us to solve this problem. They make clearly to us, which measures should be applied at any of four levels of prevention without robust spending. Primordial level of prevention should be focused to stop entering perpetrator/source of infection/reservoir of pathogen and biological agent/pathogen on defended territory. This is the first line of biodefense, deeply and multiply linked with the strategies of intelligence and deterrence. The primary prevention of biological attack is focused on monitoring and surveillance of potential internal sources of biological agents and bioterrorists. We elaborate three types of surveillance: clinical (syndromic), laboratory and environmental. Both levels of prevention were detailed analyzed, according to the next issues: Perpetrator/source of infection/reservoir of pathogen (Sophistication, Motivation, Intention, Intelligence, Secrecy, Number of perpetrators, Number of sources of infection/reservoirs, Accessibility to sources of agent/pathogen, Accessibility to targets/population at risk), Biological agent/pathogen (A category, B category, C category, Emerging pathogens, Amount of the available agent/pathogen), Means/media of delivery/factors of transmission (Air, Water, Food, Fomites, Vectors, Biological ammunition, Delivery systems, Dispersion systems mechanism of release), Target/susceptible population at risk (Intelligence, Secrecy, Personal control, Control of means/media of delivery/factors of transmission, Physical protection, Protection by chemoprophylaxis, Protection by immunoprophilaxis, Number of people in a target/population at risk, Importance of target/population at risk, Location of target/population, Distribution of people in a target/population at risk), and for each issue a whole spectrum of cheap, simple and effective preventive measures were proposed.


title: Immunosenescence and Respiratory Infections Among Nursing Home Residents

text: Residents of nursing homes are at high risk of infectious complications due to respiratory infection. The nursing home setting places residents at high risk given the frequent contact among residents and by staff along with the possibility for continuous introduction of respiratory viruses from the community. Nursing home residents are among the most frail members of society. They have multiple comorbidities that can increase their risk of infection. Immunosenescence plays an important role in not only rendering these seniors susceptible in infection, particularly viral respiratory infection, but also interferes with protection. That is, the ability to mount a robust immune response to influenza and pneumococcal vaccine increase the risk. There have been a number of T cell deficits described in this population. CD4+ T cells, in particular T-regs and CMV-reactive CD4+ T cells, have been shown to be predictive of respiratory viral infection in this population. Although evidence exists that T cell subsets may correlate better with response to vaccine and protection, antibody responses to influenza vaccine remains an important correlate in this population. Large-scale epidemiologic studies are needed to establish better correlation between biomarkers for protection and respiratory and other pathogens that circulate in nursing homes.


title: Public Education About Science in Singapore: The Role of Science Journalism via Newspapers

text: This chapter explores the role of science journalism in contributing towards public education about science in Singapore, an aspect which is under-explored in the literature. Though the key platforms for promoting public understanding of science are spearheaded mainly by institutions that promote informal science learning as well as by learned societies, the contribution from newspapers is also important. Content analysis of one continuous week of a national newspaper was undertaken, and the results show that coverage of science and technology was modest and predominantly news driven. For news stories set locally, there was a pronounced emphasis on the use of institutional actors in the text as well as quotations. Articles on health/medicine and earth science elicited the most coverage in the press. Some suggestions for using newspaper science to introduce inquiry in the science classroom are discussed.


title: Prevention and Control of Influenza Viruses

text: The 2003–2004 outbreaks of highly pathogenic avian influenza (HPAI) have proven to be disastrous to the regional poultry industry in Asia, and have raised serious worldwide public health apprehension regarding the steps that should be taken to urgently control HPAI. Control measures must be taken based on the principles of biosecurity and disease management and at the same time making public aware of the precautionary measures at the verge of outbreak. Creation of protection and surveillance zones, various vaccination strategies viz. routine, preventive, emergency, mass and targeted vaccination programmes using live, inactivated and recombinant vaccines are the common strategies adopted in different parts of the globe. The new generation vaccines include recombinant vaccines and recombinant fusion vaccine. The pro-poor disease control programmes, giving compensation and subsidies to the farmers along with effective and efficient Veterinary Services forms integral part of control of HPAI. Following biosecurity principles and vaccination forms integral part of control programme against swine and equine influenza as well. Use of neuraminidase (NA) inhibitors (Zanamivir and Oseltamivir) for the treatment of human influenza has been widely accepted worldwide. The threat of increasing resistance of the flu viruses to these antivirals has evoked interest in the development of novel antiviral drugs for influenza virus such as inhibitors of cellular factors and host signalling cascades, cellular miRNAs, siRNA and innate immune peptides (defensins and cathelicidins). Commercial licensed inactivated vaccines for humans against influenza A and B viruses are available consisting of three influenza viruses: influenza type A subtype H3N2, influenza type A subtype H1N1 (seasonal) virus strain and influenza type B virus strain. As per WHO, use of tetravaccine consisting of antigens of influenza virus serotypes H3N2, H1N1, B and H5 is the most promising method to control influenza pandemic. All healthy children in many countries are required to be vaccinated between 6 and 59 months of age. The seasonal vaccines currently used in humans induce strain-specific humoral immunity as the antibodies. Universal influenza virus vaccines containing the relatively conserved ectodomain of M2 (M2e), M1, HA fusion peptide and stalk domains, NA, NP alone or in combination have been developed which have been shown to induce cross-protection. The T cell-based vaccines are another recent experimental approach that has been shown to elicit broad-spectrum heterosubtypic immunity in the host. As far as HPAI is concerned, various pandemic preparedness strategies have been documented.


title: The Effect of Turbulence on the Spreading of Infectious Airborne Droplets in Hospitals

text: The dispersion of droplets plays an important role in the transmission of disease in a hospital environment. The challenge is that as they move, their properties change due to evaporation, the Wells (Am. J. Hyg. 20:611–618, 1934) droplet-nuclei hypothesis. In this paper we examine the effect of evaporation on their movement within a homogeneous turbulent environment. The effect of turbulence is to significantly increase the transmission distance and spread. These numerical results demonstrate that by reducing the level of turbulence, the potential for spreading diseases is reduced. This is in accordance with available experimental/in situ measurements.


title: Exacerbation of Bronchiectasis

text: Please check the hierarchy of the sections and correct if necessary.


title: Older Human B Cells and Antibodies

text: B cells have a number of different roles in the immune response. Their excellent antigen presentation potential can contribute to the activation of other cells of the immune system, and evidence is emerging that specialized subsets of these cells, that may be increased with age, can influence the cell-mediated immune system in antitumor responses. They can also regulate immune responses, to avoid autoreactivity and excessive inflammation. Deficiencies in regulatory B cells may be beneficial in cancer but will only exacerbate the inflammatory environment that is a hallmark of aging. The B cell role as antibody producers is particularly important, since antibodies perform numerous different functions in different environments. Although studying tissue responses in humans is not as easy as in mice, we do know that certain classes of antibodies are more suited to protecting the mucosal tissues (IgA) or responding to T-independent bacterial polysaccharide antigens (IgG(2)) so we can make some inference with respect to tissue-specific immunity from a study of peripheral blood. We can also make inferences about changes in B cell development with age by looking at the repertoire of different B cell populations to see how age affects the selection events that would normally occur to avoid autoreactivity, or increase specificity, to antigen.


title: Modeling Approaches Toward Understanding Infectious Disease Transmission

text: Long-standing neglected diseases continue to challenge our global health infrastructure, and emerging pathogens pose new threats worldwide. To inform prevention and response efforts, mathematical models of infectious disease dynamics are being increasingly applied. Here we explain how models can be developed to enhance our understanding and predictive power over population-level disease trends, by capturing both fundamental aspects of transmission and also the effects of medical and behavioral interventions. We review advances in transdisciplinary approaches of disease modeling and illustrate these advances with applications including community-based initiatives undertaken during the Ebola epidemic in West Africa and age-targeting of influenza vaccination in the USA. We further discuss how modern statistical inference facilitates the incorporation of data from behavioral sciences and epidemiology into models, highlighting how data-driven models can constitute powerful tools to inform and improve public health strategies.


title: Oligonucleotide Therapeutics

text: The idea of sequence-specific gene silencing by synthetic oligonucleotides targeting mRNA is at least 40 years old, but it was only in the mid-1980s when technical advances made the chemical synthesis of oligonucleotides possible that practical steps could be taken toward its implementation. The result was a deluge of experimental data in a variety of systems [1], most of which employed the phosphorothioate (PS) backbone modification, and much of which was ultimately, and unfortunately, uninterpretable.


title: Kutane Lymphome

text: Kutane Lymphome (cutaneous lymphomas: CL) umfassen die Gruppe der kutanen T-Zell-Lymphome (cutaneous T-cell lymphomas: CTCL), kutanen B-Zell-Lymphome (cutaneous B-cell lymphomas: CBCL) und die sog. hämatodermischen Neoplasien (HN). CL gehören zur Gruppe der Non-Hodgkin-Lymphome (NHL) und stellen in der Subgruppe der extranodalen NHL die zweithäufigste Gruppe hinter den gastrointestinalen Lymphomen dar (Jaffe et al. 2009). Man unterscheidet zwischen primären und sekundären CL. Primäre CL haben ihren Ursprung in der Haut und bleiben in der Regel darauf auch längere Zeit beschränkt, während sekundäre CL kutane Manifestationen von primär nodalen oder extranodalen Lymphomen darstellen (Willemze 2005). Die primären CL unterscheiden sich hinsichtlich klinischem Verlauf, Therapieoptionen und Prognose erheblich von nodalen und extrakutanen Lymphomen. So zeigen z. B. die primär kutanen CD30+-T-Zell-Lymphome einen gutartigen Verlauf, wogegen die nodalen Varianten als aggressiv eingestuft werden. Da die CL zumeist weniger aggressiv sind, werden sie auch weniger aggressiv behandelt.


title: The Contribution of Tertiary Education: Theory vs. Reality

text: Participation in education is not an end in itself. What matters for people and for our economies are the skills acquired through education. It is the competence and character qualities that are developed through schooling, rather than the qualifications and credentials gained, that make people successful and resilient in their professional and private lives. They are also key in determining individual well-being and the prosperity of societies.


title: Case Study – Germany

text: Public health structures in Germany reflect the federal system: health care in general lies within the responsibility of the 16 constituent states and the federal government only acts if a state asks for assistance. There were no bioterror-related intentional releases of biological agents in Germany in recent years. The potentially devastating effects of such an incident require sound public health preparedness planning. The Basic Constitutional Law (Grundgesetz) does not allow the deployment of armed forces within Germany with some rare exceptions. However, there is a well-established civil-military cooperation. The Federal Armed Forces (Bundeswehr) are deployed in humanitarian and multinational UN or NATO crisis containment missions abroad, requiring adequate protection from pathogens and diseases endemic or enzootic to those regions. Both, the military and the civil public health system are complex structures that contain administrative, care giving, medical investigation, and research capabilities in order to cope with natural, accidental or intentional biological incidents.


title: Terror-Related Trauma

text: In our current era, terrorist attacks have become a part of our daily life experience almost worldwide. New terrorist groups are emerging and the number of terrorist attacks is constantly rising.


title: Strategien der Distanzierung. Die späten Raumerkundungen

text: Der Anspruch ist dick unterstrichen: “Noch einmal anfangen: ganz unten, mit Fakten.”(1) Rolf Dieter Brinkmanns nach 1970 geschriebene Texte sind das Dokument einer Umorientierung, die freilich nur den immer schon vorherrschenden empirischen Aspekt des Schreibens ins Extrem treibt. Mit den Collage-Bänden Rom, Blicke (1972/73 entstanden und 1979 veröffentlicht), Erkundungen zur Präzisierung des Gefühls für einen Aufstand (1971 und im Mai 1973 entstanden, 1987 veröffentlicht) und schließlich Schnitte (März 1973 bis Juni 73 entstanden und erst 1988, 13 Jahre nach dem Tod des Autors, zur Veröffentlichung freigegeben) fand Brinkmann zu einer Form, die jegliche Rücksichtnahme darauf, wie ein ’literarischer’ Text auszusehen hat, hinter ein striktes Ziel zurückstellte: Materialien zu einer “Grundlagenforschung der Gegenwart”(2) beizutragen.


title: 7 Longaandoeningen

text: Om ziekteprocessen die zich afspelen in de longen, luchtwegen en longvliezen (pleurae) te kunnen begrijpen en de gevolgen ervan voor het functioneren van het lichaam te kunnen inschatten, is kennis nodig van de normale anatomie van de thoraxinhoud en de fysiologie van het functioneren van de long. Deze is te vinden in het boek Algemene ziekteleer uit de reeks Basiswerk, waarnaar wordt verwezen. Alleen waar nodig zal er in het kort op worden ingegaan.


title: Grid Services Complemented by Domain Ontology Supporting Biomedical Community

text: This paper describes the increasing role of ontologies in the context of Grid computing for obtaining, comparing and analyzing distributed heterogeneous scientific data. In the communities of people committed to a common goal, the management of resources and services becomes very important. We chose the application domain of human disease research and control. A characteristic of the domain is that trusted databases exist but their schemas are often poorly or not documented. The network of biomedical databases forms a loose federation of autonomous, distributed, heterogeneous data repositories ripe for information integration. Grid services will provide a dynamic way to use resources in such a large distributed scientific environment while the use of ontology enables the system to carryout reasoning at 3 levels: a) available information in all Bio-Databases (Grid nodes) worldwide, b) reasoning about the retrievable information from each node, c) reasoning about the retrieved information and presenting it in a meaningful format for users. We adopted the ontology design methodology of DOGMA and developed Generic Human Disease Ontology (GenDO) that contains common general information regarding human diseases. The information is represented in 4 “dimensions”: (a) disease types, (b) causes (c) symptoms and (d) treatments. We illustrate how this GenDO helps to produce Specific Human Disease Ontologies (SpeDO) on request. We show how the combination of two different but complementary techniques, namely Grid computing and ontology, results in a dynamic and intelligent information system. The two approaches together, being complementary, enable the system as a whole.


title: Biological Agents and Terror Medicine

text: In the last decade, terror has become an increasingly global problem. More people have become radicalized, the know-how to use weapons of mass destruction (WMD) is easily accessible by Internet and electronic media, and precursors and basic ingredients are easily purchased. Terrorists are innovative and we now face a new era of nonconventional terrorism: chemical, biological, radiological, nuclear (CBRN), as well as cyber terrorism. The deliberate use of (WMD–CBRN) by hostile states or terrorists and of naturally emerging infectious diseases that have a potential to cause illness on a massive scale could pose a national security threat.1 Resulting panic and economic damage could paralyze a country.


title: Survey on the Likely Behavioural Changes of the General Public in Four European Countries During the 2009/2010 Pandemic

text: In order to assess the likely impact of public health interventions, it is important to predict the acceptance of control measures, as well as the behavioural changes that may occur among the general public in response to epidemics, in particular lethal ones. The emergence of 2009 pandemic allowed us to assess the general public’s behaviour during the pandemic, via two surveys: one at the beginning and one after the first wave of the 2009 pandemic, in four European countries.Results showed some differences between participating countries in previous behaviours relating to seasonal flu and in beliefs and knowledge about 2009 pandemic influenza. No substantial differences were detected among the four countries in the first survey with respect to the intended behaviours in anticipation of the spread of the pandemic virus. However, results from the second survey showed differences within and among the four participating countries. The two surveys were useful in showing differences between behavioural intentions and actual actions related to the 2009 pandemic influenza. To our knowledge this is the first study investigating the actual behaviour of the population in four EU countries and provides crucial descriptions of pandemic impact on social-network dynamics parameters which can be included in mathematical models.


title: The Role of Astrocytes, Microglia, and Endothelial Cells in Coronavirus-Induced Demyelination: Induction of cytokines and other signaling mechanisms

text: Infection of neurotropic strains of coronaviruses in susceptible animals results in acute encephalomyelitis followed by a chronic demyelinating disease, similar to multiple sclerosis (MS). Although the mechanism of chronic coronavirus-induced demyelination is not entirely clear, studies show that it is mostly immune-mediated. Astrocytes, microglia and endothelial cells play an important role in normal functions as well as in immunologic and pathologic processes in the central nervous system (CNS). The interaction between coronaviruses and these cells induces various inflammatory mediators including cytokines, chemokines, MHC and NO, which acting in concert are involved in the pathogenesis of demyelination.


title: Mucosal Delivery of RNAi Therapeutics

text: The effectiveness of RNA interference-based drugs is dependent on accumulation at the target site in therapeutically relevant amounts. Local administration to the mucosal surfaces lining the respiratory, gastrointestinal and genitourinary tracts allows access into diseased areas without the necessity to overcome serum nuclease degradation, rapid renal and hepatic clearance and non-specific tissue accumulation associated with systemic delivery. This work describes RNAi therapeutics focused on pulmonary, oral, rectal and intravaginal routes of administration. Mucosal barrier components including site variations and delivery considerations are addressed in order to design an effective mucosal delivery strategy.


title: Air Purification Technology by Means of Cluster Ions Generated by Plasma Discharge at Atmospheric Pressure

text: The increased density of our living environment coupled with pollution of the atmosphere has led to a growing need for the removal of harmful molecules in the air (1). As a result research into applying a plasma discharge into the atmosphere and creating ozone and radicals of strong chemical reactivity to purify the air environment has gathered momentum. The removal of airborne particles, such as bacteria, allow for an improvement in indoor air quality so that our environment is healthy and pleasant. Within the medical field, illnesses caused by viruses such as influenza and SARS (2), hospital infections caused by airborne bacteria, fungi and allergic bronchial tube asthma (3), Japanese cedar hay fever caused by inhaling cedar pollen (4) are becoming large social concerns. In this research article, we discuss how we have applied our novel plasma discharge technology to produce positive and negative “cluster” ions. This iongenerating device operates at a normal atmospheric pressure. Subsequent investigations have permitted characterization of the resultant cluster ions. We have performed a series of experiments to prove the air purification effects of cluster ions, paying close attention to airborne harmful microbes and cedar pollen allergens.


title: Postinfectious Hemolytic Uremic Syndrome

text: Post-infectious hemolytic uremic syndrome (HUS) is caused by specific pathogens in patients with no identifiable HUS-associated genetic mutation or autoantibody. The majority of episodes is due to infections by Shiga toxin (Stx) producing Escherichia coli (STEC). This chapter reviews the epidemiology and pathogenesis of STEC-HUS, including bacterial-derived factors and host responses. STEC disease is characterized by hematological (microangiopathic hemolytic anemia), renal (acute kidney injury) and extrarenal organ involvement. Clinicians should always strive for an etiological diagnosis through the microbiological or molecular identification of Stx-producing bacteria and Stx or, if negative, serological assays. Treatment of STEC-HUS is supportive; more investigations are needed to evaluate the efficacy of putative preventive and therapeutic measures, such as non-phage-inducing antibiotics, volume expansion and anti-complement agents. The outcome of STEC-HUS is generally favorable, but chronic kidney disease, permanent extrarenal, mainly cerebral complication and death (in less than 5 %) occur and long-term follow-up is recommended. The remainder of this chapter highlights rarer forms of (post-infectious) HUS due to S. dysenteriae, S. pneumoniae, influenza A and HIV and discusses potential interactions between these pathogens and the complement system.


Diseases from Animals, Poultry, and Fish


title: Early Interventions in Allergic Diseases

text: Atopy has been defined as the genetic predisposition to develop IgE antibody responses to a variety of common environmental allergens. Clinically, atopy is expressed by asthma, allergic rhinoconjunctivitis and atopic dermatitis. It has been recognized that the “atopic march” evolves from food allergy and atopic dermatitis in the first 2 years of life, followed by asthma and allergic rhinitis. Over the past 30 years, the prevalence of allergies and asthma has increased significantly in developed countries, and asthma is one of the most common chronic diseases in children. Evidence indicates that environmental factors acting early in life, including respiratory viral infections, exposure to pets and microbial products, day-care attendance, breast feeding, and exposure to allergens, tobacco smoke and other pollutants, are key events for establishment of sensitization and development of chronic, persistent symptoms of allergic diseases [1]. It is thought that gene—environment interactions play a crucial role in these processes. Therefore, attempts to successfully prevent development of allergic diseases should be a priority. At present, there are no genetic markers for atopy or asthma which could be used routinely in clinical practice and family history of atopy has been used to identify children genetically at-risk of developing allergic diseases. These children from high-risk families have been the focus of most of the intervention studies.