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6,700
Nutrition and the Gastrointestinal System
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.
6,701
Expert-Based Scenarios for the Logistics Service Industry 2025
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.
6,702
Department of Defense Global Emerging Infections System Programs in Biodefense
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.
6,703
Nanomaterials-Based siRNA Delivery: Routes of Administration, Hurdles and Role of Nanocarriers
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.
6,704
Detection of Viral RNA Splicing in Diagnostic Virology
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.
6,705
Microfluidic Diagnostic Systems for the Rapid Detection and Quantification of Pathogens
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6,706
Il lavaggio broncoalveolare nelle pneumopatie infiltrative diffuse
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.
6,707
Global Issues and Health Interactions: Reflexions from the South
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.
6,708
Investigating Protein Adsorption via Spectroscopic Ellipsometry
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.
6,709
Biologics
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.
6,710
Recent Experiences in Parameter-Free Data Mining
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.
6,711
Flu or a Bug?
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.
6,712
Virology
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!
6,713
Great Plagues of the Past and Remaining Questions
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.
6,714
Multiplex PCR in Molecular Differential Diagnosis of Microbial Infections: Methods, Utility, and Platforms
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.
6,715
Physiologie und Pathophysiologie der Zelle
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.
6,716
Cardiovascular Anatomy and Pharmacology
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.
6,717
Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery
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.
6,718
Noninvasive Mechanical Ventilation: Models to Assess Air and Particle Dispersion
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.
6,719
Bioinformatics and Translation Elongation
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.
6,720
Viren mit einzelsträngigem, segmentierten RNA-Genom in Negativstrangorientierung
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).
6,721
Detection of Bovine Coronavirus by Conventional Reverse Transcription Polymerase Chain Reaction
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.
6,722
Drug Development Research
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).
6,723
Mitochondria and Antiviral Immunity
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).
6,724
Advocating Global Health Security
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.
6,725
DNA, RNA und IHRE Amplifikation
DNA heißt die magische Helix des Lebens — der materielle Träger der Erbsubstanz, die Desoxyribonucleinsäure (DNA, deoxyribonucleic acid) (siehe Box 6.1).
6,726
Alcohol and HIV: Experimental and Clinical Evidence of Combined Impact on the Lung
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.
6,727
Schlafkrankheitserreger
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6,728
Gastroenteric Viruses
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.
6,729
The Discovery Process of SFTS in China
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.
6,730
Social Network Analysis for Contact Tracing
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.
6,731
Acute and chronic liver insufficiency
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.
6,732
Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis
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.
6,733
Computational Vaccinology
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.
6,734
Primordial and Primary Levels of Biothreat and Bioterrorism Prevention
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.
6,735
Immunosenescence and Respiratory Infections Among Nursing Home Residents
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.
6,736
Public Education About Science in Singapore: The Role of Science Journalism via Newspapers
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.
6,737
Prevention and Control of Influenza Viruses
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.
6,738
The Effect of Turbulence on the Spreading of Infectious Airborne Droplets in Hospitals
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.
6,739
Exacerbation of Bronchiectasis
Please check the hierarchy of the sections and correct if necessary.
6,740
Older Human B Cells and Antibodies
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.
6,741
Modeling Approaches Toward Understanding Infectious Disease Transmission
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.
6,742
Oligonucleotide Therapeutics
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.
6,743
Kutane Lymphome
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.
6,744
The Contribution of Tertiary Education: Theory vs. Reality
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.
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Case Study – Germany
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.
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Terror-Related Trauma
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.
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Strategien der Distanzierung. Die späten Raumerkundungen
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.
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7 Longaandoeningen
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.
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Grid Services Complemented by Domain Ontology Supporting Biomedical Community
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.
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Biological Agents and Terror Medicine
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.
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Survey on the Likely Behavioural Changes of the General Public in Four European Countries During the 2009/2010 Pandemic
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.
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The Role of Astrocytes, Microglia, and Endothelial Cells in Coronavirus-Induced Demyelination: Induction of cytokines and other signaling mechanisms
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.
6,753
Mucosal Delivery of RNAi Therapeutics
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.
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Air Purification Technology by Means of Cluster Ions Generated by Plasma Discharge at Atmospheric Pressure
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.
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Postinfectious Hemolytic Uremic Syndrome
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.
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Diseases from Animals, Poultry, and Fish
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6,757
Early Interventions in Allergic Diseases
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.
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Comparative Considerations and Conclusions
The noteworthy success of a small embargoed island in scientific development, and in particular in a typically US-dominated and capital-intensive sector like biotechnology, has attracted considerable interest and discussion among the analysts and specialists, since it shows features that are unique in the panorama of developing countries. Cuba’s achievements in science and technology seem an exception with respect to what usually happens in other underdeveloped countries, excluded probably the biggest and richest ones. Even more exceptional is the development of biotechnology in Cuba. Some concepts are summarized, inspired form the most competent specialists in the field.
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Infectieziekten
In dit hoofdstuk komen kliniek, diagnostiek en behandeling van de belangrijkste infectieziekten bij kinderen aan de orde.
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Sarkosporidiose
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6,761
Gene Therapy for Lung Diseases
Gene therapy is under development for a variety of lung disease, both those caused by single gene defects, such as cystic fibrosis and α(1)-antitrypsin deficiency, and multifactorial diseases such as cancer, asthma, lung fibrosis, and ARDS. Both viral and nonviral approaches have been explored, the major limitation to the former being the inability to repeatedly administer, which renders this approach perhaps more applicable to conditions requiring single administration, such as cancer. Progress in development and clinical trials in each of these diseases is reviewed, together with some potential newer approaches for the future.
6,762
Efficient Parameterized Algorithm for Biopolymer Structure-Sequence Alignment
Computational alignment of a biopolymer sequence (e.g., an RNA or a protein) to a structure is an effective approach to predict and search for the structure of new sequences. To identify the structure of remote homologs, the structure-sequence alignment has to consider not only sequence similarity but also spatially conserved conformations caused by residue interactions, and consequently is computationally intractable. It is difficult to cope with the inefficiency without compromising alignment accuracy, especially for structure search in genomes or large databases. This paper introduces a novel method and a parameterized algorithm for structure-sequence alignment. Both the structure and the sequence are represented as graphs, where in general the graph for a biopolymer structure has a naturally small tree width. The algorithm constructs an optimal alignment by finding in the sequence graph the maximum valued subgraph isomorphic to the structure graph. It has the computational time complexity O(k (t) N (2)) for the structure of N residues and its tree decomposition of width t. The parameter k, small in nature, is determined by a statistical cutoff for the correspondence between the structure and the sequence. The paper demonstrates a successful application of the algorithm to developing a fast program for RNA structural homology search.
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Noninvasive Ventilation in Patients with Severe Acute Respiratory Syndrome
Severe acute respiratory syndrome first emerged in Guangdong, China in November 2002 and then spread rapidly to many countries through Hong Kong in 2003 [1–4]. A 64-year-old physician from southern China, who had visited Hong Kong on February 21, 2003 and died 10 days later of severe pneumonia, is believed to have been the source of infection causing subsequent outbreaks of severe acute respiratory syndrome (SARS) in Hong Kong, Vietnam, Singapore, and Canada [1–4]. By the end of the epidemic in July 2003, there had been 8,096 cases reported in 29 countries and regions, with a mortality incidence of 774 (9.6 %) [5]. Among the 8,096 cases, 1,706 were health care workers (HCWs). A novel coronavirus (CoV) was responsible for SARS [6]. Bats are likely the natural reservoirs of SARS-like CoV [7, 8].
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Imaging of Lung Transplantation
Lung transplantation has become a viable treatment option for end-stage lung disease. Common indications for lung transplantation are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension. Either single or bilateral lung transplantation can be performed, but bilateral lung recipients appear to have a better median survival than single lung recipients. Complications after lung transplantation are common and may have nonspecific clinical and radiologic manifestations. The time point at which these complications occur relative to the date of transplant is crucial in formulating a differential diagnosis and recognizing them accurately. Significant advances in imaging techniques and recognition of air trapping in exhalation images and other patterns /distribution of parenchymal abnormalities have led to routine use of HRCT for diagnostic evaluation in patients manifesting respiratory decline in the lung transplant recipient.
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3 Infecties van de onderste luchtwegen en tuberculose
Tot de onderste luchtwegen behoren alle onderdelen van de luchtwegen en longen onder de stembanden (trachea, bronchi en bronchioli).
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Infections: The Emergency of the New Millennium
The New Millennium opened with alarming data on infections and antimicrobial resistance. Viral infections (SARS, MERS-CoV, Zika, Chikungunya, West Nile, Ebola virus infection, etc.) emerged or re-emerged with threatening outbreaks. However, viral emerging infections in some instances represented marginally a concern for developed countries that were just lapped by them. Currently, the new emergency is represented by antimicrobial resistance in bacterial infections, that is, a matter of extreme importance in developed and developing countries, where this issue has become a top priority for global policy makers and public health authorities. New mechanisms of resistance continue to emerge and spread globally, threatening our ability to treat common infections. The overuse and misuse of antimicrobials both in the human and animal field, and their dispersion in the environment pose a risk for selection of mechanisms of resistance of germs. Some settings, like the healthcare facilities, where the use of antimicrobials is obviously intense and infection prevention and control can be poor, represent the reservoir for multidrug-resistant organisms and, sometimes, the melting pot for pan-resistant strains.
6,767
Hematologic Complications
Critically ill patients are at high risk of developing various hematologic complications that may be present on admission or occur during their stay in the Intensive Care Unit (ICU). Often times the etiology of specific hematologic abnormalities is unclear and the diagnosis may be challenging due to the complexity of critically ill patients. This chapter will focus on diagnosis and management of the most commonly encountered hematologic problems in the critically ill such as anemia, neutropenia, thrombocytopenia, coagulopathy and thrombotic complications, with specific focus on diagnosis and management of these conditions.
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Molecular Virology
Traditional viral isolation by cell culture assays and conventional serological methods have been previously used to detect and identify various virus infections
6,769
Schützengrabenfieber
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6,770
Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges
Diagnosis and identification of viruses is an important component of diagnostic virology laboratory. Although various modes of diagnostic methods are now available at disposal, a vast majority of the diseases across the globe remain undiagnosed. This is largely due to the overlapping undifferentiated set of symptoms across myriad set of RNA and DNA viral diseases. As such, it becomes critical to take into consideration several factors for viral diagnosis ranging from the type and quality of specimen collected, time of specimen collection, mode of transport, accuracy, specificity, sensitivity, and the type of diagnostic method used. This chapter broadly emphasizes various methods on diagnostic virology ranging from the classical methods of diagnosis to the most recently developed molecular methods of detection of virus.
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Il versamento pleurico: aspetti eziologici, diagnostici e clinici
Il coinvolgimento della pleura puÒ comparire nel corso di molteplici e differenti patologie. Le cause che sottendono un versamento pleurico possono essere intra-toraciche o sistemiche e, se in alcuni casi queste appaiono facilmente individuabili grazie a segni clinici patognomonici, in altri casi l’inquadramento nosografico di un versamento puÒ risultare complesso, dovendosi basare su elementi clinici e reperti laboratoristico-strumentali spesso aspecifici.
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Bioinformatics Applications in Advancing Animal Virus Research
Viruses serve as infectious agents for all living entities. There have been various research groups that focus on understanding the viruses in terms of their host-viral relationships, pathogenesis and immune evasion. However, with the current advances in the field of science, now the research field has widened up at the ‘omics’ level. Apparently, generation of viral sequence data has been increasing. There are numerous bioinformatics tools available that not only aid in analysing such sequence data but also aid in deducing useful information that can be exploited in developing preventive and therapeutic measures. This chapter elaborates on bioinformatics tools that are specifically designed for animal viruses as well as other generic tools that can be exploited to study animal viruses. The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. Various databases that organize information on animal and human viruses have also been described. The chapter will converse on overview of the current advances, online and downloadable tools and databases in the field of bioinformatics that will enable the researchers to study animal viruses at gene level.
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Current Capabilities of First Responders in Different Countries
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25 Keel-, neus- en oorheelkunde
Bovensteluchtweginfecties, recidiverende middenoorontstekingen en tonsillitiden behoren tot de meest frequent voorkomende ziektebeelden bij kinderen. Mede door het veranderde beloop, de verminderde morbiditeit en vernieuwde inzichten zijn de behandelstrategieën de afgelopen jaren veranderd. Een afwachtend beleid, watchful waiting, lijkt nu veelal aangewezen.
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Recent Advances in Real-time Mass Spectrometry Detection of Bacteria
The analysis of bio-aerosols poses a technology challenge, particularly when sampling and analysis are done in situ. Mass spectrometry laboratory technology has been modified to achieve quick bacteria typing of aerosols in the field. Initially, aerosol material was collected and subjected off-line to minimum sample treatment and mass spectrometry analysis. More recently, sampling and analysis were combined in a single process for the real-time analysis of bio-aerosols in the field. This chapter discusses the development of technology for the mass spectrometry of bio-aerosols, with a focus on bacteria aerosols. Merits and drawbacks of the various technologies and their typing signatures are discussed. The chapter concludes with a brief view of future developments in bio-aerosol mass spectrometry.
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Pneumonia
The lung is constantly exposed to airborne infectious agents due to the large surface area of approximately 100 m(2). Therefore pneumonia is one of the most common lung diseases. Understanding infection requires understanding the routes of infections, the way invading organisms infect epithelial cells, as well as defense mechanisms of the lung tissue acquired during evolution. Different variants of infectious and non-infectious pneumonias are discussed; special types of pneumonias such as granulomatous and fibrosing pneumonias are presented under separate sections. Causing organisms and other causes of pneumonias are included, and their mode of action is included as far as understood.
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Acute Exacerbation of COPD
Acute exacerbations of COPD involve increased symptoms such as cough, dyspnea and sputum production. These exacerbations are associated with increased mortality as well as decline in lung function. Non-invasive positive-pressure ventilation (NIPPV) is the preferred method of ventilatory support in respiratory failure secondary to AECOPD. NIPPV reduces work of breathing, improves oxygenation and ventilation and decreases both mortality and the risk of invasive ventilation. Other therapies for AECOPD include inhaled bronchodilators and systemic glucocorticoids. Antibiotics are recommended for severe exacerbations. Future areas of interest in treatment for AECOPD include utilization of biomarkers and extracorporeal carbon dioxide removal.
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Tuberculosis in the Intensive Care Unit: The North American Perspective
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6,779
Infectious Complications of Cancer Therapy
Advances in the management of cancer, particularly the development of new chemotherapeutic agents, have greatly improved the survival and outcome of patients with hematologic malignancies and solid tumors; overall 5-year survival rates in cancer patients have improved from 39% in the 1960s to 60% in the 1990s.1 However, infection, caused by both the underlying malignancy and cancer chemotherapy, particularly myelosuppressive chemotherapy, remains a persistent challenge.
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Globalisation and its Effects on Educational Leadership, Higher Education and Educational Policy
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6,781
Sarcoptes scabiei
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The Origin and Evolution of Viruses
The lecture covers three main topics: (i) Viruses: properties, place in the living world, and possible origin; (ii) Molecular basis of viral variability and evolution; and (iii) Evolution of viral pathogenicity and emerging viral infections.
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Quasispecies Dynamics of RNA Viruses
RNA viruses, such as human immunodeficiency virus, hepatitis C virus, influenza virus, and poliovirus replicate with very high mutation rates and exhibit very high genetic diversity. The extremely high genetic diversity of RNA virus populations originates that they replicate as complex mutant spectra known as viral quasispecies. The quasispecies dynamics of RNA viruses are closely related to viral pathogenesis and disease, and antiviral treatment strategies. Over the past several decades, the quasispecies concept has been expanded to provide an adequate framework to explain complex behavior of RNA virus populations. Recently, the quasispecies concept has been used to study other complex biological systems, such as tumor cells, bacteria, and prions. Here, we focus on some questions regarding viral and theoretical quasispecies concepts, as well as more practical aspects connected to pathogenesis and resistance to antiviral treatments. A better knowledge of virus diversification and evolution may be critical in preventing and treating the spread of pathogenic viruses.
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Ungewissheit, Uneindeutigkeit, Unsicherheit – Braucht die Theorie reflexiver Modernisierung eine neue Handlungstheorie?
Moderne Zeiten sind unsichere Zeiten – so lautet der Befund soziologischer Gegenwartsdiagnosen. Die Theorie reflexiver Modernisierung hat diesen Befund weiter zugespitzt. Sie diagnostiziert, dass die Gesellschaft, in der wir leben – die Zweite Moderne – durch Ungewissheit, Uneindeutigkeit und Unsicherheit gekennzeichnet ist: Entscheidungen beruhen nicht mehr auf gesichertem Wissen, soziale Lagen lösen sich auf und vertraute Institutionen wie der Nationalstaat oder die Erwerbsarbeit verlieren ihre Konturen. Während Institutionen, Organisationen und Individuen mehr denn je dazu gezwungen sind, Entscheidungen zu treffen, wird dies gleichzeitig immer schwieriger, denn institutionalisierte Entscheidungskonventionen produzieren Nebenfolgen, die die Basisinstitutionen moderner Gesellschaften bedrohen. „Die Turbulenzen, die … auf allen Handlungsebenen und in allen Handlungskontexten entstehen, bilden das Schlüsselproblem für Gegenwart und Zukunft der Zweiten Moderne und das zentrale Thema ihrer Erforschung“ (Beck/Bonß/Lau 2004: 15).
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Systemic Syndromes with Biomedicines
Since the introduction of biomedicines in human therapy, a number of systemic reactions have been more frequently reported as important adverse events following treatment. Some monoclonal antibodies, interleukins, receptor inhibitors, and growth factors may preferably induce acute, violent, early events with an overall low frequency, but with serious and life-threatening capacity. .
6,786
Pandemic Risk Modelling
This chapter will explore the nature of communicable diseases, a brief history of pandemics, and will introduce the mathematical models used to evaluate the risk pandemics pose to human populations. Such modelling is used in a public health context, where modelling past and current events provides insight in how to respond most effectively to a new outbreak. It is also used in the context of risk mutualisation and transfer. As recently as 2013, a survey of 30,000 insurance executives placed global pandemic as the biggest extreme risk facing insurers (Towers Watson. 2013. Insurers Rate Global Pandemic as the Major Extreme Risk. 3 December). The chapter will introduce the principles used to model these events in the insurance industry and will conclude with a review of the way these models are applied in an unconventional risk transfer context.
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Management of Malignant Pleural Effusions
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Clinical Application of Stem/Stromal Cells in COPD
Chronic obstructive pulmonary disease (COPD) is a progressive life-threatening disease that is significantly increasing in prevalence and is predicted to become the third leading cause of death worldwide by 2030. At present, there are no true curative treatments that can stop the progression of the disease, and new therapeutic strategies are desperately needed. Advances in cell-based therapies provide a platform for the development of new therapeutic approaches in severe lung diseases such as COPD. At present, a lot of focus is on mesenchymal stem (stromal) cell (MSC)-based therapies, mainly due to their immunomodulatory properties. Despite increasing number of preclinical studies demonstrating that systemic MSC administration can prevent or treat experimental COPD and emphysema, clinical studies have not been able to reproduce the preclinical results and to date no efficacy or significantly improved lung function or quality of life has been observed in COPD patients. Importantly, the completed appropriately conducted clinical trials uniformly demonstrate that MSC treatment in COPD patients is well tolerated and no toxicities have been observed. All clinical trials performed so far, have been phase I/II studies, underpowered for the detection of potential efficacy. There are several challenges ahead for this field such as standardized isolation and culture procedures to obtain a cell product with high quality and reproducibility, administration strategies, improvement of methods to measure outcomes, and development of potency assays. Moreover, COPD is a complex pathology with a diverse spectrum of clinical phenotypes, and therefore it is essential to develop methods to select the subpopulation of patients that is most likely to potentially respond to MSC administration. In this chapter, we will discuss the current state of the art of MSC-based cell therapy for COPD and the hurdles that need to be overcome.
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Transfusion and Acute Respiratory Distress Syndrome: Clinical Epidemiology, Diagnosis, Management, and Outcomes
Transfusion related acute lung injury (TRALI) is a life-threatening complication of blood product transfusion. It is the leading cause of blood product transfusion related death in the USA. The syndrome is defined by hypoxemic respiratory failure with bilateral infiltrates on chest X-ray in the setting of a blood transfusion and absence of cardiac failure. The exact incidence of TRALI is unknown, but the incidence is higher in the critically ill patient population. Multiple patient and donor related risk factors for TRALI exist, including critically illness, alcohol use, and receiving transfusions with high plasma volumes. Practitioners should have a low index of suspicion for the diagnosis of TRALI, and blood bank reporting is vital to aid in diagnosis and future prevention. Management is primarily supportive care, with supplemental oxygen as the mainstay for therapy. Despite the transient course of TRALI, its morbidity is severe with the majority of patients requiring mechanical ventilation and treatment in the intensive care unit. For patients that survive TRALI, outcomes are promising without residual pulmonary deficits. Prevention strategies over the past 10 years have helped to decrease the incidence of TRALI and have led to increased awareness of this condition in the medical field.
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The RPE Cell and the Immune System
The RPE cell plays a pivotal role in retinal immunity. In fact, the RPE cell orchestrates both innate and adaptive immunity and contains a plethora of factors to regulate the immune response. Many immunoregulatory activities of the RPE cell are accomplished through cytokine production, toll-like receptor (TLR) activation, complement regulation and antigen presentation. The RPE cells immune regulatory network plays an essential role in retinal immunity and autoimmunity, retinal infections and in a variety of retinal degenerative disorders. Understanding the immune regulatory properties of this cell may provide additional clues to disease mechanisms that may lead to future treatments for many human retinal diseases.
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Fibrinogen (FI)
Das Hauptsubstrat der Gerinnung ist Fibrinogen (FI). Bei akuter Blutung ist es zumeist der erste Gerinnungsfaktor, der kritische Grenzwerte erreicht (150–200 mg/dl). FI kann hervorragend mittels point-of-care-tauglicher viskoelastischer Methoden (Thrombelstographie oder Thrombelastometrie) monitiert werden. Die Substitution kann mittels Frischplasma, Cryopräzipitat oder Fibrinogenkonzentrat erfolgen. Frischplasma ist nicht besonders effektiv, mit einer erhöhten Morbidität, insbesondere bei kritisch Kranken, sowie mit Volumenbelastung assoziiert. Cryopräzipitat wird in einigen europäischen Ländern nicht angeboten. Die Gabe von Fibrinogenkonzentrat wird in verschiedenen Leitlinien empfohlen. Als Akut-Phase-Protein kann FI physiologischerweise bei Entzündungsprozessen, schweren Verletzungen sowie nach großen Operationen in kurzer Zeit auf über 1000 mg/dl ansteigen; wobei hier Fibrinogenspaltprodukte anti-inflammatorische und sogar antibakterielle Eigenschaften haben.
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Healthy Cities: Old and New Solutions
Cities have had historically higher mortality and morbidity rates than rural areas. These spiked dramatically after the Industrial Revolution, which led to the first health of cities movement that stimulated the adoption of new public health measures to improve the built-environment in the developed countries. Together with such additional factors as increasing prosperity, hygiene and especially medical advances, the old health disadvantages of cities was reversed. But a new set of medical challenges threatening to reverse previous progress has emerged. These include such problems as bacterial resistances to many of the drugs that reduced communicative diseases, to the effects of indoor living and aging, all of which require urgent attention. In addition, a review of the various health determinants that contribute to ill-health shows that since many of these factors are not within the prevue of current medical practice, they must be addressed if the health and well-being of people in cities are to be improved. A series of other problems that were previously overlooked are being tackled by the new Healthy Cities movement, such as the need for more political and citizen involvement in planning and delivering health care, better ways of promoting health rather than just curing ill-health with a new emphasis on wellness, as well as more effective measures to reduce the persistent pockets of ill-health in many cities.
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A New Method of Differentiation Between a Biological Attack and Other Epidemics
The main obstacle in identifying a biological attack (BA), while preventing false alarms, epidemics of panic and unnecessary expenditures is the insufficient data on which to rely. Тhis new method of outbreak analysis is based on our original model of bioterrorism risk assessment. The intention was to develop a model of quick and accurate evaluation of an unusual epidemiologic event (UEE) that would save time, money, human and material resources and reduce confusion and panic. This UEE analysis is a subtle and detailed differentiation through assessment of BA feasibility in comparison with three other types of outbreak scenarios. There are two types of differences between these four scenarios: qualitative and quantitative. Qualitative and quantitative differences are defined with 23 and 10 indicators, respectively. Both types of indicators can have three different values: N/A, 0 or 1. We have carried out a feasibility analysis for subtle and detailed differentiation among four outbreak scenarios. As a tool for feasibility analysis we have introduced a “system of elimination”. System elimination is applied if one component contains all indicators scored with 0 or as N/A – the related scenario is then eliminated from further consideration. The system was applied to four UEEs: (1) an intentional attack by a deliberate use of a biological agent (Amerithrax), (2) a spontaneous outbreak of a new or re-emerging disease (“swine flu”), (3) a spontaneous outbreak by an accidental release of a pathogen (Sverdlovsk anthrax), and (4) a spontaneous natural outbreak of a known endemic disease that may mimic bioterrorism or biowarfare (Kosovo tularemia). It was found that “agent” was the most important and the most informative UEE component of the new scoring system. This system might be helpful in the analysis of unusual epidemic events and a quick differentiation between biological attacks and other epidemics.
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Metabolische Störungen
Bei fortgeschrittenem Organversagen von Niere, Herz, Leber oder Lunge stellt eine Organtransplantation meist das einzige kurative Therapieverfahren dar. Auch eine Knochenmarktransplantation wird bei sonst unheilbaren Leukämien oder Lymphomen eingesetzt. Nach Organtransplantation treten bei 30–60% der Patienten neurologische Komplikationen auf. Differenzialdiagnostisch müssen vorbestehende, durch die Grunderkrankung bedingte, Störungen von intraoperativen Komplikationen, von metabolisch bedingten neurologischen Störungen und von Nebenwirkungen der notwendigen immunsuppressiven Medikation abgegrenzt werden. Immunsuppressiva können dabei sowohl eine direkte Neurotoxizität als auch indirekt vermehrt Infektionen des Zentralnervensystems (ZNS) und sekundäre ZNS-Malignome verursachen. Während metabolische Enzephalopathien oder opportunistische ZNS-Infektionen bei allen Patienten nach Transplantation etwa gleich häufig auftreten können, sind andere neurologische Syndrome für bestimmte Organtransplantationen typisch.
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Infectious Diseases
This chapter contains four tables on infectious diseases. It features tables on common causes of fever in the ICU, prevention and management of hospital-acquired and ventilator-associated pneumonias.
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Mykobakterien, nichttuberkulöse (NTM)
Atypische, ubiquitäre, Umwelt-Mykobakterien, „Mycobacteria other than Mycobacterium tuberculosis“ MOTT
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Molecular Epidemiology, Genomics, and Phylogeny of Crimean-Congo Hemorrhagic Fever Virus
Crimean-Congo hemorrhagic fever virus (CCHFV) constitutes a group of viruses of the genus Nairovirus (family Bunyaviridae). Like all members of the Bunyaviridae, the genome of CCHFV is composed of tripartite single-stranded RNA. These segments, designated small (S), medium (M), and large (L), minimally encode the nucleocapsid (N), envelope glycoproteins (Gn and Gc), and RNA-dependent RNA polymerase (RdRp), respectively [38].
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Infektionen des Respirationstrakts
Infektionen des Respirationstrakts sind die meistverbreiteten Infektionserkrankungen des Menschen. Vor allem eine Erkältungserkrankung stellt sicherlich eine der häufigsten Ursachen für eine ärztliche Konsultation dar.
6,799
Glocal English in Singapore? A Re-exploration of the Localization of English
This chapter re-considers the notion of ‘glocal English’ or ‘glocalism’ in discussing the use of English in Singapore. As a global language, English has developed in interesting ways via social media and the Internet all over the world. However, it is only in special polities such as Singapore where it is used as the ‘working language’ of the country for a multilingual population base, that English has developed into a phenomenon that has to be studied, better understood and perhaps given a label such as ‘glocal English.’ The chapter will contribute to the ongoing discussions of what it means for English to be a global language and how it adapts as ‘a communicative tool of immense political, ideological, and economic power’(Kachru, Kontalinguistik, 1996, pp. 906–913) in global-local tensions (e.g. commerce, trade, finance, industry, science and technology versus intra-ethnic and inter-ethnic communication within Singapore). In the shifting perspectives of what English is (really global or truly local?), what it does (for and in education), and how it is used in this country (globally and/or locally), the paper hopes to elucidate the dimensions of teaching and learning English in the Singapore context and perhaps more widely in an Asia-Pacific context.