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7,600 |
Severe Infections in the Returning Traveler
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The ease of air travel has made spread of infectious agents a global problem. There are a multitude of tropical diseases ranging from benign viral illnesses to highly contagious and life-threatening diseases and it is important to take a detailed clinical and travel history from the ill returning traveller, especially in the fi rst 4 weeks of return.
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7,601 |
Adverse Transfusion Reactions in Critically Ill Patients
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Although transfusion therapy in the past 30 years has achieved high levels of safety, severe adverse reactions can still complicate a red blood cell, plasma, or platelet transfusion. Adverse events can be either of infectious nature (Infectious Adverse Reactions to Transfusion–IARTs) or noninfectious (NIARTs). The former are due to viruses, bacteria, or protozoa present in the transfused component. Medical doctors faced with an infectious disease in a hospitalized patient should always collect an accurate clinical history that must include transfusion of blood components and take into consideration that the viral/bacterial/protozoan infection could be related to a transfusion event. If a transfusion-transmitted infection is suspected, the clinician must contact the transfusion center that will provide a look-back of the blood products and a follow-up of the involved donors. NIARTs may be of immunological and nonimmunological nature. This chapter provides an overview of pathogenesis, presentation, therapy, and prevention of the main NIARTs. Finally, organizational measures for the management of NIARTs are presented, in order to ensure the highest possible level of safety for the patients.
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7,602 |
Autoimmune Encephalitis in the Intensive Care Unit
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Autoimmune encephalitis is a rapid, progressive encephalopathy due to an autoimmune response directed against the brain parenchyma. It is associated with significant morbidity, often necessitating evaluation and treatment in the intensive care unit (ICU). Patient management centers on rapid diagnosis of the autoimmune encephalitis syndrome with careful assessment for other etiologies of acute encephalopathy, the initiation of immunosuppressive therapy, and the management of associated sequelae including status epilepticus, respiratory failure, elevated intracranial pressure, and dysautonomia.
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7,603 |
Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety
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Vaccine science has extended beyond genomics to proteomics and has come to also encompass ‘immunomics,’ the study of the universe of pathogen-derived or neoplasm-derived peptides that interface with B and T cells of the host immune system. It has been theorized that effective vaccines can be developed using the minimum essential subset of T cell and B cell epitopes that comprise the ‘immunome.’ Researchers are therefore using bioinformatics sequence analysis tools, epitope-mapping tools, microarrays, and high-throughput immunology assays to discover the minimal essential components of the immunome. When these minimal components, or epitopes, are packaged with adjuvants in an appropriate delivery vehicle, the complete package comprises an epitope-based immunome-derived vaccine. Such vaccines may have a significant advantage over conventional vaccines, as the careful selection of the components may diminish undesired side effects such as have been observed with whole pathogen and protein subunit vaccines. This chapter will review the pre-clinical and anticipated clinical development of computer-driven vaccine design and the validation of epitope-based immunome-derived vaccines in animal models; it will also include an overview of heterologous immunity and other emerging issues that will need to be addressed by vaccines of all types in the future.
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7,604 |
1 Zorgvuldig en verantwoord handelen in de basiszorg
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In dit hoofdstuk besteden we aandacht aan zorgvuldig en verantwoord handelen, veiligheid, vrijheidsbeperkende maatregelen, hygiëne en infectiepreventie en ergonomisch werken. Deze belangrijke onderwerpen zijn van toepassing op zorgsituaties van de gezondheidspatronen van Gordon die in de diverse hoofdstukken aan de orde komen. Kennis hiervan is van belang voor de basisverpleegkunde.
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7,605 |
Norovirus and Other Viral Gastroenteritis
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New and old entero-pathogenic viruses are increasing in the society and in the healthcare, like the Calicivirus family (Norovirus, Sapovirus, Astrovirus), Reovirus family (Rotavirus) (especially infant, toddler and elderly) and rarely other viral types such as adenovirus (especially serotype 40, 41), bocavirus, parechovirus, enterovirus and a variety of other types. In all types of gastroenteritis, infection prevention measures are performed as with norovirus, described below. The following chapter is focused on practical measures to detect and prevent transmission of entero-pathogenic viruses in healthcare institutions.
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7,606 |
Supply Chain Risk Management: A Neural Network Approach
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Effective supply chain risk management (Hallikas et al. 2002; Harland et al. 2003; Henke et al. 2006) requires the identification, assessment and monetization of risks and disruptions, as well as the determination of the probability of their occurrence and the development of alternative action plans in case of disruptions (cf. Zsidisin 2003; Zsidisin et al. 2004; Zsidisin et al. 2000; Vidal a. Goetschalckx, 2000). Companies traditionally use multiple sources for material procurement and/or hold safety stocks to avoid vulnerability. However, these strategies can negatively impact the supply chain performance, leading to higher purchase and logistics costs. The aim of this chapter is to illustrate how the implementation of the supply chain risk management concept can be improved by using a neural network approach.
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7,607 |
Automated Knowledge Extraction from Internet for a Crisis Communication Portal
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This paper describes the development of an Automated Knowledge Extraction Agent (AKEA) which was designed to acquire online news and document from the internet for the establishment of a knowledge based crisis communication portal. It was recognized that in times of crisis, an effective communication mechanism is essential to maintain peace and calmness in the community by providing timely and appropriate information. It is proposed that the incorporation of software agents into the crisis communication portal will be capable to send alert news to subscribed users via internet and mobile services. The proposed system consists of crawler, wrapper, name-entity tagger, AIML (Artificial Intelligence Markup language) and an animated character is used in the front-end for human computer communication.
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7,608 |
Infectious Disease Epidemiology
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The following chapter intends to give the reader an overview of the current field of applied infectious disease epidemiology. Prevention of disease by breaking the chain of transmission has traditionally been the main purpose of infectious disease epidemiology. While this goal remains the same, the picture of infectious diseases is changing. New pathogens are identified and already known disease agents are changing their behavior. The world population is aging; more people develop underlying disease conditions and are therefore more susceptible to certain infectious diseases or have long term sequelae after being infected.
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7,609 |
Chirurgische Infektionen
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Der menschliche Organismus ist von einer unzähligen Menge von Mikroorganismen umgeben. Dringen diese Krankheitserreger in uns ein, dann laufen Wechselbeziehungen zwischen dem Eindringling und dem Wirtsorganismus ab. Krankheit resultiert, wenn die Mikroorganismen aufgrund ihrer verschiedenen Determinanten der Pathogenität und Virulenz den Wettlauf mit der Infektabwehr des Makroorganismus gewonnen haben. Mit diesem Problem hatten sich Chirurgen zu allen Zeiten auseinanderzusetzen—und es hat bis heute nicht an Aktualität verloren.
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7,610 |
The Antiviral Potential of Host Protease Inhibitors
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The replication of numerous pathogenic viruses depends on host proteases, which therefore emerged as potential antiviral drug targets. In some cases, e.g., for influenza viruses, their function during the viral propagation cycle is relatively well understood, where they cleave and activate viral surface glycoproteins. For other viruses, e.g., Ebola virus, the function of host proteases during replication is still not clear. Host proteases may also contribute to the pathogenicity of virus infection by activating proinflammatory cytokines. For some coronaviruses, human proteases can also serve in a nonproteolytical fashion simply as receptors for virus entry. However, blocking of such protein-protein contacts is challenging, because receptor surfaces are often flat and difficult to address with small molecules. In contrast, many proteases possess well-defined binding pockets. Therefore, they can be considered as well-druggable targets, especially, if they are extracellularly active. The number of their experimental crystal structures is steadily increasing, which is an important prerequisite for a rational structure-based inhibitor design using computational chemistry tools in combination with classical medicinal chemistry approaches. Moreover, host proteases can be considered as stable targets, and their inhibition should prevent rapid resistance developments, which is often observed when addressing viral proteins. Otherwise, the inhibition of host proteases can also affect normal physiological processes leading to a higher probability of side effects and a narrow therapeutic window. Therefore, they should be preferably used in combination therapies with additional antiviral drugs. This strategy should provide a stronger antiviral efficacy, allow to use lower drug doses, and minimize side effects. Despite numerous experimental findings on their antiviral activity, no small-molecule inhibitors of host proteases have been approved for the treatment of virus infections, so far.
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7,611 |
Preventie, gezondheidsbescherming en -bevordering
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Preventieve voorzieningen kunnen, voor zover ze bij menselijk gedrag aanknopen, op het individu of op collectiviteiten zijn gericht.(1) Individuele preventie vindt onder andere plaats in het kader van de relatie tussen de patiënt en de behandelend arts, bijvoorbeeld als er een dieet wordt voorgeschreven, een leefadvies of erfelijkheidsadvisering wordt gegeven. Maar ook curatieve activiteiten kunnen een individueel preventief aspect hebben, voor zover ze verergering van ziekte of de gevolgen van een ziekte beogen te voorkomen. Deze individuele preventieve activiteiten blijven in dit hoofdstuk buiten beschouwing.
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7,612 |
Microorganisms and Biotic Interactions
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Most ecosystems are populated by a large number of diversified microorganisms, which interact with one another and form complex interaction networks. In addition, some of these microorganisms may colonize the surface or internal parts of plants and animals, thereby providing an additional level of interaction complexity. These microbial relations range from intraspecific to interspecific interactions, and from simple short-term interactions to intricate long-term ones. They have played a key role in the formation of plant and animal kingdoms, often resulting in coevolution; they control the size, activity level, and diversity patterns of microbial communities. Therefore, they modulate trophic networks and biogeochemical cycles, regulate ecosystem productivity, and determine the ecology and health of plant and animal partners. A better understanding of these interactions is needed to develop microbe-based ecological engineering strategies for environmental sustainability and conservation, to improve environment-friendly approaches for feed and food production, and to address health challenges posed by infectious diseases. The main types of biotic interactions are presented: interactions between microorganisms, interactions between microorganisms and plants, and interactions between microorganisms and animals.
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7,613 |
Pathogenesis of Fever
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The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response. The hypothalamic thermoregulatory centre accomplishes heat production by inducing shivering and heat conservation through vasoconstriction. At an established degree, fever is regulated (even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set point. Therefore fever does not climb up relentlessly. In addition to the function as an endogenous pyrogen, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever. The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the host’s survival during infection.
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7,614 |
The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis
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Apoptosis is a fundamental process contributing to tissue homeostasis, immune response, and development. CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNFR) superfamily. Its ligand, CD95L, was initially detected at the plasma membrane of activated T-lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Given its implication in immune homeostasis and immune surveillance combined with the fact that various lineages of malignant cells exhibit loss-of-function mutations, CD95 was initially classified as a tumor suppressor gene. Nonetheless, in different pathophysiological contexts, this receptor is able to transmit non-apoptotic signals and promote inflammation and carcinogenesis. Although the different non-apoptotic signaling pathways (NF-κB, MAPK, and PI3K) triggered by CD95 are known, the initial molecular events leading to these signals, the mechanisms by which the receptor switches from an apoptotic function to an inflammatory role, and, more importantly, the biological functions of these signals remain elusive.
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7,615 |
Ultrastructural Telepathology: Remote EM Diagnostic via Internet
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The digital revolution has given rise to new tools in different disciplines of science; much of this new knowledge has been assimilated into different telemedicine applications and also extends the boundaries of pathology, a diagnostic medical discipline. The tissue-based pathologic diagnosis is the gold standard for all subsequent medical procedures - especially surgery and tumour treatment - and electron microscopy, owing to its high-resolution, can provide significant data not discernible by light microscopy to render the correct diagnosis. In case of diagnostic difficulty remote experts can instantly examine pathologic samples directly using an ultrastructural telepathology system: the consulting “second opinion” expert is no longer constrained by problems inherent in preselected images. Growing Internet bandwidth and developing Grid technology foster such interactive telemicroscopy solutions enabling savings of time and resources in healthcare, research and distance teaching.
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7,616 |
Terror Medicine: Education and Training
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If a mass casualty incident (MCI) occurs on American territory, the main difficulty with disaster response is not from a lack of resources or volunteers but from a lack of a properly managed disaster plan. In fact, first responders and local healthcare practitioners, and even non-clinical locals rush to the scene and to local healthcare facilities to offer their services or make donations. The presence of so many volunteers and donations can be of great help during a disaster if properly managed. Even before 9/11, hospitals were required to have a disaster plan and ensure that their employees were familiar with it. Very few hospitals, however, actually worked on coordinating their disaster response plans with other hospital facilities, Emergency Medical Services (EMS), or local governmental facilities to offer a united response in case of a disaster.(1) Healthcare institutions therefore had difficulties not only working with other institutions preparing for a disaster but also were often unprepared for managing unexpected resources from the community.
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7,617 |
Fungal, Viral, and Other Oddball Infections and the Immunosuppressed Patient
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Infections with fungal and viral pathogens in the surgical intensive care unit (ICU) are not uncommon. Often, however, diagnosis tends to be either delayed or superimposed on bacterial infections. In some scenarios, definitive diagnosis can be challenging and a high index of suspicion is warranted to promptly manage critically ill patients. This approach is critical especially in immunosuppressed patients given their relative vulnerability to a multitude of infectious processes. Although rare, oddball infections with rare viruses and fungi can significantly affect the clinical course and recovery of patients if timely diagnosis is delayed. This chapter highlights important fungal, viral, and rare infections in the context of critically ill and high-risk patients, including the immunosuppressed patients, in the surgical ICU.
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7,618 |
Pharmacology of Chloroquine and Hydroxychloroquine
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The 4-aminoquinolines are weak bases that are completely absorbed from the gastrointestinal tract, sequestered in peripheral tissues, metabolized in the liver to pharmacologically active by-products, and excreted via the kidneys and the feces. The parent drugs and metabolites are excreted with a half-life of elimination of approximately 40 days. However, slow release from sequestered stores of the drugs means that after discontinuation, they continue to be released into the plasma for years. Correct dosing is based on the ideal body weight of the patient, which depends on height. The 4AQs diminish autoimmunity without compromising immunity to infections.
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7,619 |
Viral Processes by Random Walks on Random Regular Graphs
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We study the SIR epidemic model with infections carried by k particles making independent random walks on a random regular graph. We give a edge-weighted graph reduction of the dynamics of the process that allows us to apply standard results of Erdős–Renyi random graphs on the particle set. In particular, we show how the parameters of the model produce two phase transitions: In the subcritical regime, O(ln k) particles are infected. In the supercritical regime, for a constant C determined by the parameters of the model, Ck get infected with probability C, and O(ln k) get infected with probability (1 − C). Finally, there is a regime in which all k particles are infected. Furthermore, the edge weights give information about when a particle becomes infected. We demonstrate how this can be exploited to determine the completion time of the process by applying a result of Janson on randomly edge weighted graphs.
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7,620 |
Trench-Fieber
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7,621 |
Potential Impact of Climate Change on Pandemic Influenza Risk
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Health problems related to the environment continue to be a major source of concern all over the world. Society needs to develop measures that will eliminate or considerably reduce hazardous factors from the environment that can result in health risk to humans.
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7,622 |
The Age of Transformation
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The world is going through a transformation. We face a number of tremendous societal challenges for which traditional approaches no longer work. Mankind has gone through big changes before: moving from the agricultural economy to the industrial economy, and more recently, into the ‘experience’ economy and the knowledge economy. This chapter explores the paradigm shifts of the past and the present, to set the scene for the rest of the book. Most of all, facing the current societal challenges will require collaboration between profit and non-profit organizations as well as connected individuals, to create meaningful innovations that will guide people and society through the transformation.
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7,623 |
Andrographolide
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Andrographolide is a diterpene lactone compound extracted from Andrographis paniculata (Burm. F) Nees, which is commonly used as traditional Chinese medicine. Andrographolide has effects of anti-inflammatory, antibacterial, antivirus, antitumor, and immune regulation and is used in treatment of cardiovascular-cerebrovascular diseases and protection of the liver and gallbladder. Andrographolide water solubility is poor and its bioavailability is low; its pharmacological effects are extensive but weak, so the preparation requirements are strict.
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7,624 |
Now and Future Practice
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In the past 11 chapters, we have visited some heroes, diseases, and treatments that are part of the heritage of the healing professions, we have discussed some of the language of medicine and some thoughts of our most erudite predecessors, and we have examined some instances of clinical practice, including a few times when what happened was not what we today would have wished. I hope that the 231 pages that we have traveled together so far have convinced you of the rich and (usually) honorable traditions of medicine. The tales are sometimes epic, at times tragic, sporadically triumphant, and occasionally lamentable. This last chapter suggests some ways that you, as a health professional or informed consumer, will now—I hope—learn more about medicine’s history and lore.
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7,625 |
Helminth
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Strongyloides stercoralis, an intestinal nematode commonly known as the human threadworm, affects millions of people worldwide.(1) It is endemic in Southeast Asia, Latin America, sub-Saharan Africa, and parts of the southeastern USA.(2) In the USA, the highest prevalence rates are found in eastern Kentucky and rural Tennessee. A unique feature of Strongyloides stercoralis infection is the occurrence of an autoinfection cycle which permits persistence of the parasite years after the normal host has left an endemic area. In this cycle, the rhabditiform larvae in the duodenojujenal portion of the small intestine transform directly into filariform (infective) larvae. The filariform larvae without leaving the body can reinfect the patient by penetrating the intestinal mucosa. This distinctive characteristic of Strongyloides, to persist and replicate within the host for decades, produces minimal or no symptoms. Immunocompromised patients may develop a fulminant illness due to a unique process in the life cycle of Strongyloides in which there are dramatic increases in the number of filariform larvae. In the hyperinfection syndrome, massive numbers of larvae migrate through the intestinal mucosa and into the lungs (the usual migration pattern) and disseminate to involve other organ systems not ordinarily a part of the life cycle of the parasite. Larvae may be found in the central nervous system, kidneys, liver, and almost any other organ.
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7,626 |
Noninvasive Positive-Pressure Ventilation in Patients with Acute Hypoxemic Respiratory Failure and HIV/AIDS
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Pulmonary complications, especially acute respiratory failure (ARF), contribute to morbidity and mortality in immunocompromised patients. The etiology, pathophysiology, and reversibility of lung injury and the severity of ARF are key to the therapeutic response and prognosis for these patients.
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7,627 |
Arguing from Ignorance
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It might seem that it can never be rational to argue from a state of ignorance. But this is not the case. Ignorance arguments abound in our everyday thinking such as when we conclude that a train does not stop in York because York is not listed in the timetable. These arguments also tend to be the first line of defence when the safety of food or prescribed medications is called into question. The statement ‘There is no evidence that beef is unsafe’, which is a premise in an ignorance argument, was used so extensively by health officials and government ministers during the BSE epidemic in the UK that it came to be called the mantra of the BSE affair by the public inquiry into the epidemic. A similar ignorance premise is often used to frame the conclusion of systematic reviews into the effectiveness of a particular medical or health intervention. This chapter examines the various purposes for which ignorance arguments are advanced in medicine and health and considers the epistemic conditions under which these arguments are more or less rationally warranted.
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7,628 |
Risico’s, melden en controles
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Waar mensen werken worden fouten gemaakt. Ze raken door routine soms hun alertheid kwijt of hebben door tijdgebrek de nodige hygiënische maatregelen overgeslagen. Ook krijgen veel zorgverleners een slecht voorbeeld van collega’s: handen worden slecht gewassen en slecht gedroogd, zo blijkt uit diverse onderzoeken.
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7,629 |
Maintenance of Preparedness
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The medical management of patients with highly hazardous communicable diseases (HHCD) will suddenly become important during public health emergencies of international concern but will receive little attention in between those events. It is very important to use those times to maintain and improve the level of preparedness and adjust it to advances in the field. The infrastructure provided needs to be regularly adjusted but also requires intensive maintenance. Every high-level isolation unit (HLIU) needs to plan individually and very precisely what kind of equipment, materials and medications need to be stockpiled and in what amount, in order to be able to provide adequate care. Providing HLIU treatment is a highly qualified and differentiated task, and training efforts should provide a multidisciplinary HLIU team with an intricate training schedule. The medical and psychological aspects of occupational health and safety need to be addressed as well in order to maintain preparedness.
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7,630 |
Common Cold and Flu
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Most of the causative agents of the common cold are viruses. The respiratory system consists of an air conduction portion and a respiratory portion. The direct initiating factor of the common cold is low temperature, especially relative coldness. When people feel cold or chilly, vascular constriction around the inlet area of air occurs, resulting in a reduction of mucus secretion containing various antiviral soluble mediators and followed by an explosive increase in the nasal viral flora. A relatively low temperature and dryness are good conditions for viral proliferation and invasion to the body. The first symptom of the common cold is usually a runny nose, followed by a sore throat and/or systemic fever. Acute symptoms of the common cold are usually terminated within 3 days, at the longest 5~7 days. The mortality rate of severe acute respiratory syndrome (SARS) has reached around 10%. A novel swine-origin influenza A (H1N1) virus caused the occurrence of more than 130,000 patients and dead cases of more than 800 people. H5N1 avian influenza showed an extremely high mortality rate, even though its infectivity is low. A new serotype of AI (H7N9) has appeared in some areas of China. Vitamin C can prevent the onset of a cold. Vitamin C can even prevent influenza virus from spreading down from the upper respiratory tract to the lower one. In addition, levels of interferon (IFN) in the bronchoalveolar lavage (BAL) fluid are markedly low in vitamin C-insufficient mice. Inflammatory cells are markedly increased in BAL fluid, providing the immunological evidences that daily supplementation of high-dose vitamin C can prevent influenza infection and that, in extreme case, it can save the life.
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7,631 |
Biomaterial and Therapeutic Applications
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Sepsis, a condition in which the bloodstream is fighting a systemic infection, is a major health concern in both developed and developing countries.
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7,632 |
Toward Control of Infectious Disease: Ethical Challenges for a Global Effort
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Despite the devastating pandemic of HIV/AIDS that erupted in the early 1980s, despite the failure to eradicate polio and the emergence of resistant forms of tuberculosis that came into focus in the 1990s, and despite newly emerging diseases like Severe Acute Respiratory Syndrome (SARS) in 2003 and the fearsome prospect of human-to-human avian flu, it is nevertheless a time of some excitement over prospects for effective control of much of infectious disease. Funded by national and international governmental and nongovernmental organizations (NGOs), private foundations, and even popular entertainers, large-scale new efforts are under way to address global killers like AIDS, tuberculosis, and malaria, among others. This “marvelous momentum” can be seen as part of a continuing effort from the time of Jenner onward. Extrapolating from this, we explore the notion of a “comprehensive global effort for the eradication, elimination or control of infectious disease,” with particular attention to the ethical issues that arise. This is to “think big” about disease-control efforts that are now often done in piecemeal ways. This chapter identifies five tracks along which such efforts need to be pursued: (1) national and international organizations and the development of collective will; (2) epidemiological and health care infrastructure; (3) scientific development; (4) religious, social, and cultural considerations; (5) legal and social protections for individuals and groups. Each of these poses significant ethical issues which, we argue, should be viewed in a comprehensive way, to ensure that practice, research, and policy in each of these areas understands the person with communicable infectious disease as both victim and (potential) vector.
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7,633 |
The Application of Nucleic Acid Amplification Strategies in Theranostics
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Targeting nanoparticles equipped with diagnosis “tools” to malignant cells or tissues for optimal therapy is a popular concept of theranostics. As one of the most reliable and sensitive diagnosis “tools,” nucleic acid detection is of growing practical interest with respect to molecular diagnostics of cancer and other genetic diseases. Particularly, PCR-based and other nucleic acid amplification strategies are most widely used in theranostics. This chapter aims at systematization and critical summarization of the applications of DNA- or RNA-targeted nucleic acid amplification strategies in theranostics.
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7,634 |
Bead-Based Flow Cytometric Assays: A Multiplex Assay Platform with Applications in Diagnostic Microbiology
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Researchers have focused on developing specific assays for conclusively identifying and measuring the levels of bacteria, fungi, protozoa, viruses (microbes), and their associated products (biomarkers) that cause disease in humans and animals (Murray et al., 2003). Traditional methods using microscopy and chemical or immunological stains, test cultures with selective media or target cells, or serological assays have been used effectively to identify infectious agents in biological specimens or environmental samples. However, due to increasing veterinary, medical, and public health concerns, faster and more accurate diagnostic tools have been sought. Multiplex array-based assays allow for a range of biomarkers to be rapidly and simultaneously measured within specimens (Robertson and Nicholson, 2005). Recently, multiplex bead-based flow cytometric immunoassays have been developed and applied that show great promise for improving the study, diagnosis, and therapeutic management of infectious diseases (Alvarez-Barrientos et al., 2000; Jani et al., 2002).
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7,635 |
The Role of Receptor for Advanced Glycation Endproducts (RAGE) in Infection
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During evolution, multicellular organisms have developed an impressive arsenal of defense and repair mechanisms to counteract threats such as infection and trauma. Such an inflammatory response begins with the detection of the potential life-threatening event by recognizing so-called danger signals. These signal molecules have been classically divided into: i) Exogenous, pathogen-associated molecular patterns (PAMPs) [1], which are conserved motifs on pathogens that are not found in higher eukaryocytes; and ii) endogenous innate danger molecules, also named damage-associated molecular patterns (DAMPs) or alarmins, which are structurally diverse proteins rapidly released by the host itself during infection or (sterile) tissue damage [2].
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7,636 |
Respiratory Tract and Mediastinum
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Normal cytology, abnormal and atypical cells, non-cellular components, and infectious cell changes are largely described together with benign, malignant, and neuroendocrine lesions regarding exfoliative and aspiration cytology of the lung. A separate section broadly addresses diagnostic findings and differential diagnoses in bronchoalveolar washings. The section ‘Fine needle aspiration biopsy of mediastinal disorders’ covers in particular biopsy techniques, accuracy of liquid-based cytology, and the complex lesions of the thymus gland. Cytodiagnostic algorithms of the major benign and malignant pulmonary and mediastinal lesions and their respective differential diagnoses are additionally presented in synoptic setups.
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7,637 |
STICHWORTVERZEICHNIS
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7,638 |
Rapid Detection of Viruses Using Loop-Mediated Isothermal Amplification (LAMP): A Review
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Most of the diseases caused by viral infection are found to be fatal, and the diagnosis is difficult due to confusion with other causative agents. So, a highly efficient molecular-based advance detection technique, i.e., loop-mediated isothermal amplification (LAMP) method, is developed for diagnosis of viral infections by various workers. It is based on amplification of DNA at very low level under isothermal conditions, using a set of four specifically designed primers and a DNA polymerase with strand displacement activity. This technique is found to be superior than most of the molecular techniques like PCR, RT-PCR, and real-time PCR due to its high specificity, sensitivity, and rapidity. Major advantage of LAMP method is its cost-effectiveness as it can be done simply by using water bath or dry bath. Here, in this review information regarding almost all the effective LAMP techniques which is developed so far for diagnosis of numerous viral pathogens is presented.
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7,639 |
Infecties van de bovenste luchtwegen
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Luchtweginfecties in het algemeen en infecties van de bovenste luchtwegen in het bijzonder komen wereldwijd zeer veel voor en zijn de voornaamste reden om een arts te consulteren. In de niet-geïndustrialiseerde landen zijn luchtweginfecties bovendien nog steeds de belangrijkste doodsoorzaak op de kinderleeftijd. Infecties van de bovenste luchtwegen worden meestal veroorzaakt door virussen, en ook zijn er bacteriële verwekkers. Deze behoren meestal tot de eigen flora; S. pneumoniae is de belangrijkste. Op klinische gronden kan geen onderscheid worden gemaakt tussen de verschillende verwekkers van bovenste luchtweginfecties. Antibiotische behandeling van bovenste luchtweginfecties is slechts zelden nodig. Etiologische laboratoriumdiagnostiek voor influenza-achtige ziektebeelden is vooral van belang bij risicogroepen en in gezondheidsinstellingen vanwege de beschikbaarheid van antivirale behandeling en eventuele maatregelen ter voorkoming van nosocomiale verspreiding van influenzavirussen. Jaarlijkse griepvaccinatie is geïndiceerd bij risicogroepen ter voorkoming van een ernstig ziektebeloop en bij gezondheidswerkers ter voorkoming van nosocomiale verspreiding. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_2) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.
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7,640 |
Impfungen
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Bedeutung. Impfungen sind die wichtigsten und kosteneffektivsten Präventivmaßnahmen der modernen Medizin. Mit der breiten Nutzung von Vakzinen hat die Inzidenz der impfpräventablen Infektionskrankheiten in den vergangenen Jahrzehnten weltweit dramatisch abgenommen. Trotz der nachgewiesenen Erfolge sind die Bedenken der Öffentlichkeit gegenüber potenziellen Risiken von Impfstoffen gewachsen und bestimmen heute in hohem Maße Akzeptanz und Nutzung von Impfungen. Öffentliche Impfempfehlungen stellen ein dynamisches Gleichgewicht zwischen Risiken und Vorteilen von Impfungen dar. Unverändert sind Impfungen der sicherste und beste Weg, Gesundheitsvorsorge zu betreiben und Infektionskrankheiten zu kontrollieren.
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NIAID International Research Programs: Global Impact
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NIAID conducts and supports a global program of research aimed at improving diagnosis, treatment, and prevention of immunologic, allergic, and emerging infectious diseases. This research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world (http://www3.niaid.nih.gov/topics/GlobalResearch/default.htm)
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Rule Generation Using NN and GA for SARS-CoV Cleavage Site Prediction
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Cleavage site prediction is an important issue in molecular biology. We present a new method that generates prediction rules for SARS-CoV protease cleavage sites. Our method includes rule extraction from a trained neural network and then enhancing the extracted rules by genetic evolution to improve its quality. Experimental results show that the method could generate new rules for cleavage site prediction, which are more general and accurate than consensus patterns.
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White-Collar Crimes and the Fear of Crime: A Review
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Biomarker Development in Chronic Inflammatory Diseases
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Chronic inflammatory diseases, such as inflammatory bowel disease—namely, Crohn’s disease and ulcerative colitis—psoriasis, multiple sclerosis, rheumatoid arthritis, and many others affect millions of people worldwide, causing a high burden of disease, socioeconomic impact, and healthcare cost. These diseases have common features including autoimmune pathogenesis and frequent co morbidity. The treatment of these chronic inflammatory diseases usually requires long-term immunosuppressive therapies with undesirable side effects. The future of chronic inflammatory disease prevention, detection, and treatment will be greatly influenced by the use of more effective biomarkers with enhanced performance. Given the practical issues of collecting tissue samples in inflammatory diseases, biomarkers derived from body fluids have great potential for optimized patient management through the circumvention of the abovementioned limitations. In this chapter, peripheral blood, urine, and cerebrospinal fluid biomarkers used in chronic inflammatory conditions are reviewed. In detail, this chapter reviews biomarkers to fore used or emerging to be used in patients with chronic inflammatory conditions. Those include inflammatory bowel diseases, chronic inflammatory conditions of the liver, biliary tract, pancreas, psoriasis, atopic disease, inflammatory skin diseases, rheumatic diseases, demyelination, and also the chronic inflammatory component of various other diseases in general medicine—including diabetes, cardiovascular disease, renal disease, and chronic obstructive pulmonary disease. Development of personalized medicine is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery, and monitoring of diseases.
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Sepsis
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The management of the child with sepsis represents the sine qua non of pediatric critical care medicine. Overwhelming sepsis and septic shock often manifest with concurrent derangements of cardiovascular function, intravascular volume status, respiratory function, immune regulation, renal function, coagulation, hepatic function, and metabolic function – sepsis literally affects every organ system to some degree. The degree to which any of these derangements are manifest in a given child is highly variable and influenced by multiple host and pathogen factors, including the child’s developmental stage, the presence or absence of co-morbidities, the host’s immune/inflammatory state, the host’s genetic background, and the specific pathogens involved. These factors combine, in turn, to profoundly influence the ultimate outcome. Successful management of critically ill children depends upon early recognition, early treatment with antibiotics, and early reversal of shock.
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Le infezioni da Papillomavirus
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Evidenze epidemiologiche molecolari indicano che il DNA di almeno uno dei 15 tipi oncogeni di Papillomavirus umano (HPV) viene rilevato virtualmente in tutte le lesioni carcinomatose e che l’infezione persistente da HPV ad alto-rischio è la causa necessaria ma non sufficiente per il processo carcinogenico. Sebbene il rilevamento di DNA di HPV in tutte le lesioni cancerose non sia prova definitiva del suo ruolo causale nella carcinogenesi, è stato valutato che il rischio relativo di cancro associato con i genotipi oncogeni di HPV è addirittura più alto del rischio di carcinoma polmonare associato con il fumo. In natura sono stati identificati più di 120 genotipi di HPV, di cui circa 40 possono infettare il tratto genitale; di questi, 15 sono fortemente associati al cancro della cervice. Il meccanismo biologico di trasformazione maligna è stato ben caratterizzato. In sintesi, il potenziale oncogenico di questi virus è legato ai geni virali E6 e E7. La oncoproteina virale E6 inizia la degradazione della proteina anti-oncogenica (p53), mentre la oncoproteina virale E7 porta all’inattivazione di un’altra proteina di soppressione tumorale (RB). Questi effetti sinergici sono passaggi importanti della carcinogenesi in quanto danno luogo alla perdita del controllo del ciclo cellulare. Sulla base della loro presenza in lesioni benigne o maligne della cervice, questi virus sono stati definiti come HPVs a basso, medio od alto rischio oncogeno. Gli HPV vengono tipicamente trasmessi nelle donne entro pochi anni dall’inizio della loro attività sessuale e, prevalentemente, sono causa di infezioni transitorie e clinicamente irrilevanti che nella maggior parte dei casi si risolvono spontaneamente senza alcuna conseguenza patologica e con cambiamenti citologici temporanei. Fortunatamente, a seguito dell’infezione primaria, soltanto una minoranza di donne mantiene una infezione persistente (circa il 10% dopo 5 anni) ed è questo gruppo più piccolo che ha un sostanziale rischio (più del 50%) di sviluppare lesioni precancerose ad alta malignità (HSIL) o, in assenza di uno screening efficace, il carcinoma della cervice (CC) uterina.
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Chronic Lung Pathologies That Require Repair and Regeneration
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Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks.
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Approach to the Febrile Patient in the Intensive Care Unit
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Fever occurs in approximately one-third of all medical patients during their hospital stay and in more than 90% of critically ill patients with severe sepsis [1]. According to the Society of Critical Care Medicine (SCCM) and the Infectious Diseases Society of America (IDSA), a temperature above 38.3°C (101°F) should be considered as fever necessitating a clinical assessment. The mean body temperature in healthy individuals is 36.8°C (98.2 °F), with a range of 35.6°C (96°F) to 38.2°C (100.8 °F) and a slight diurnal/circadian variation of between 0.5 and 1.0°C [2, 3]. Patients with elevated temperature in the ICU are in a closed monitoring system undergoing accurate and reproducible measurements using a variety of methods (instruments and techniques) at different body sites (Table 1.1) [4].
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The Way Forward: Prevention, Treatment and Human Rights
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There now is a considerable body of evidence to support the view that an effective HIV/AIDS strategy integrates prevention, treatment and human rights. In this chapter, we emphasize the importance of each of these aspects and draw upon the conclusions reached in previous chapters to map out the future of HIV/AIDS. While medicine and science have a crucial role to play in addressing pandemics, whether slow-moving (like HIV/AIDS) or fast-moving (like influenza), the social, legal, political, financial and economic ramifications of pandemics can not be ignored. Well-considered social, legal, political and financial strategies are essential in order to address any pandemic effectively.
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Introduction: Human Security Development and the Future of East Asia
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For more than a decade, a group of North Koreans have languished in a legal gray zone: Despite being prima facie refugees, they have not been accorded refugee status in accordance with international law. These North Koreans, most famously personified by their daring escapades into foreign consulates in China, are not unknown to the authorities. But the United Nations High Commission for Refugees (UNHCR) and the governments of China, Russia, and the two Koreas have instead chosen to pursue a less politically messy agenda of sweeping it under the proverbial carpet. Despite the adoption of the human security agenda by the international community, these refugees who have fled North Korea to escape the widespread starvation and poverty brought about by large-scale famines since the 1990s seem to have fallen through the gaps. This chapter examines the efficacy, or the lack thereof, of the human security paradigm in the nexus between politics and refugees. Any attempt to resolve the matter can only begin with a re-conceptualization of the entire security paradigm, including the adoption of “sustainable security,” and to perceive human security as an ethos to pave way for a more constructive political culture of reconciliation instead of recrimination.
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Infektionsimmunologie
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Im Laufe der Entwicklung der Lebewesen traten die Organismen gegeneinander in Konkurrenz und entdeckten andere Spezies als eigene Lebensgrundlage oder Nahrung. Bei höheren Lebewesen sehen wir dies als selbstverständlich an und teilen Sie in Fleisch- und Pflanzenfresser ein. Bei niederen Lebewesen bezeichnen wir dies jedoch als pathogene Eigenschaft oder als parasitäre Lebensweise, wenn wir ihnen als Nahrungsgrundlage dienen (Abb. 8.1). Zur Abwehr der Krankheitserreger entwickelten alle höheren Lebewesen ein Immunsystem, um das Fortbestehen der Spezies zu garantieren. Je weiter sich die Lebewesen entwickelt haben, desto höher hat sich auch das Immunsystem in einer Coevolution in Konkurrenz zu den Erregern entwickelt. Da das Immunsystem in der Evolution zur Infektionsabwehr entstanden ist, leiten sich seine übrigen physiologischen und pathophysiologischen Mechanismen von denen der Infektionsabwehr ab.
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Text Mining the Biomedical Literature for Identification of Potential Virus/Bacterium as Bio-Terrorism Weapons
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There are some viruses and bacteria that have been identified as bioterrorism weapons. However, there are a lot other viruses and bacteria that can be potential bioterrorism weapons. A system that can automatically suggest potential bioterrorism weapons will help laypeople to discover these suspicious viruses and bacteria. In this paper we apply instance-based learning & text mining approach to identify candidate viruses and bacteria as potential bio-terrorism weapons from biomedical literature. We first take text mining approach to identify topical terms of existed viruses (bacteria) from PubMed separately. Then, we apply a text mining method bridge these terms as instances with the remaining viruses (bacteria) and thus to discover how much these terms describe the remaining viruses (bacteria). In the end, we build an algorithm to rank all remaining viruses (bacteria). We suspect that the higher the ranking of the virus (bacterium) is, the more suspicious they will be potential bio-terrorism weapon. Our findings are intended as a guide to the virus and bacterium literature to support further studies that might then lead to appropriate defense and public health measures.
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Discovery of the Proprotein Convertases and their Inhibitors
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The members of the convertase family play a central role in the processing of various protein precursors ranging from hormones and growth factors to viral envelope proteins and bacterial toxins. The proteolysis of these precursors that occurs at basic residues is mediated by the proprotein convertases (PCs), namely: PC1, PC2, Furin, PACE4, PC4, PC5 and PC7. The proteolysis at non-basic residues is performed by subtilisin/kexin-like isozyme-1 (S1P/SKI-1) and the newly identified neural apoptosis-regulated convertase-1 (NARC-1/PCSK9). These proteases have key roles in many physiological processes and various pathologies including cancer, obesity, diabetes, neurodegenerative diseases and autosomal dominant hypercholesterolermia. Here we summarize the discovery of the proprotein convertases and their inhibitors, discuss their properties, roles, resemblance and differences
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Cyanine Dye–Nucleic Acid Interactions
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Cyanine dyes are widely used in biotechnology due to their ability to form fluorescent complexes with nucleic acids. This chapter describes how the structure of the dye determines the mode in which it binds to nucleic acids as well as the fluorescence properties of the resulting complexes. Related dyes, such as hemicyanines and styryl dyes, are briefly described as well. In addition, covalent conjugates of cyanines with nucleic acids or with nucleic acid-binding ligands allow fluorescent labeling and probing of DNA/RNA structure and function. Several examples of different types of conjugates and their applications are described.
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T Cells in Viral Infections: The Myriad Flavours of Antiviral Immunity
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Viral diseases are a major cause of morbidity and mortality and result in a significant public health burden. T lymphocytes first identified in the chordate lineage and constitute a highly sophisticated branch of adaptive immune system. Apart from B cells, it is the only cell type that exhibits antigenic specificities; achieved by gene rearrangement. T cells are unique with respect to diversity of their subsets, which have distinct effector specificities, proliferative abilities, memory generation, and life span. T cells are impactful in viral infections by virtue of their capability to combat intracellular pathogens. The effector functions of T cells are mediated through cytokines/chemokines and by direct cytotoxicity of infected cells. T cell response can be beneficial or detrimental to host; prognosis depending on qualitative and quantitative differences in the response. Persistent viral infections are associated with functionally suboptimal, exhausted T cell responses, which are unable to clear virus. Specific subsets such as regulatory T cells (Tregs) dampen antiviral responses; thereby favouring viral persistence. However, Tregs protect the host from immunopathology by limiting perpetual inflammation. Certain other subsets such as Th17 cells may contribute to autoimmune component of viral infections. The importance of T cells is highlighted by the fact that modern vaccination and therapeutic approaches focus on modulating T cell frequencies and effector functions. This chapter emphasises the understanding how T cells influence outcomes of viral infections, modern vaccination and therapeutic strategies with thrust on T cell biology.
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Environment Problems in the Coastal Zone
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Understanding coastal dynamics and natural history is important in developing a better understanding of natural systems and human impacts in coastal zones. This chapter outlines the characteristics of sedimentary environments in coastal zones which must be understood in order to manage and preserve coastal environments.
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Dietary Phytochemicals Target Cancer Stem Cells for Cancer Chemoprevention
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Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Cancer progression ends in tumor metastasis to distant sites, and metastasis is the major reason for cancer patient deaths. Recent experimental evidence suggests the pivotal role of cancer stem cells. A tumor is heterogeneous and composed of different cell types. The cancer stem cells in the tumor have the capacity both to self-renew and differentiate to sustain the tumor. Features of cancer stem cells are described in this review, with an emphasis on the role that dietary phytochemicals may play in cancer chemoprevention. Ingredients in the diet can inhibit cancer cells and cancer stem cells. These compounds include curcumin from curry, epigallocatechin gallate from green tea, resveratrol from red wine, genistein from soy, sulforaphane from broccoli, and many others. Current research findings advocate the beneficial effects towards cancer chemoprevention via uptake of a combination of different dietary phytochemicals.
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Febrile Neutropenia in Transplant Recipients
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Febrile neutropenic patients are at increased risk of developing infections. During the initial stages of neutropenia, most of these infections are bacterial. The spectrum of bacterial infections depends to some extent on whether or not patients receive antimicrobial prophylaxis when neutropenic. Since most transplant recipients do, Gram-positive organisms predominate, due to the fact prophylaxis is directed primarily against Gram-negative organisms. Staphylococcus species (often methicillin-resistant), Streptococcus species (viridans group streptococci, beta-hemolytic streptococci), and Enterococcus species (including vancomycin-resistant strains) are isolated most often. Therefore, potent empiric Gram-positive coverage is recommended by many in this setting. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species are the most common Gram-negative pathogens isolated. Non-fermentative Gram-negative bacilli (Stenotrophomonas maltophilia, Acinetobacter species) are emerging as important pathogens. Many of these organisms acquire multiple mechanisms of resistance that render them multidrug resistant. The administration of prompt, broad-spectrum, empiric, antimicrobial therapy is essential and is generally based on local epidemiology and susceptibility/resistance patterns. Response rate to the initial regimen is generally in the range of 75–85%. Fungal infections develop in patients with prolonged neutropenia (greater than 7–10 days). Candida species and Aspergillus species are the predominant fungal pathogens, although many other fungi are opportunistic pathogens in this setting. Fungal infections are seldom documented microbiologically or on histopathology, and the administration of empiric antifungal therapy, when such infections are suspected, is the norm. Therapy is often prolonged, and outcomes are still suboptimal. The importance of infection control and antimicrobial stewardship cannot be overemphasized.
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Acquired Nonneoplastic Neonatal and Pediatric Diseases
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The lung biopsy is an established procedure to procure a pathologic diagnosis in a child with a suspected pneumonic process of undetermined etiology. Improvements in pediatric anesthesia and surgery have reduced the operative complications to a minimum. A biopsy can usually be taken through a small intercostal incision when localization is not especially important in a patient with diffuse changes (see Chapter 1). The alternative method for tissue sampling is the endoscopic transbronchial biopsy. There is less risk to the patient, but the specimen is smaller and crush artifacts from the instrument are more common.
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Human Rights and State Responsibilities
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This chapter lays out an argument that citizens’ human rights are the responsibility of the corresponding State, meaning that citizens of a territorial State claim particular rights that State is obliged to deliver. In return, in an aspect which is often neglected in analyses of human security, citizens also owe allegiance to the State. Citizens’ rights have been expanded to encompass not only physical protection within a territory but also a host of economic and welfare provisions. Despite the increasingly international discourse on human security rights, their legal home remains with the national State vis-à-vis its citizens. The chapter argues that the rules of the State-based order are shifting, with no clear loci of responsibility and accountability for human security.
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Pandemics and Dual-Use Research
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Biological risks and threats come in many forms which can contribute to the globalisation of insecurity. The end of the twentieth century saw increased momentum to reframe infectious diseases from purely health issues to those of security concern. HIV/AIDS, SARS, bird flu, and swine flu pandemics in the twenty-first century have challenged nation-states and international institutions. Added to this challenge are the developments and breakthroughs in scientific experiments. While such progress has the potential to eradicate disease and improve human well-being, it also has the potential to present new risks and possible threats to society if the knowledge is used inappropriately. Biological dual-use research can inherently have both beneficial and dangerous consequences. Several incidents have highlighted the potential dangers associated with scientific experiments such as the accidental creation of the highly virulent mousepox, the reconstruction of the 1918 influenza virus, and the manipulation of the H5N1 bird flu virus. Almost all items necessary to produce lethal biological agents are dual-use and can be readily found in pharmaceutical laboratories. The ability to obtain a pathogen, weaponise the agent, and employ or disperse it, needs to be considered in terms of capability and intent and the increasing franchisation of terrorist groups such as Al Qaeda. The availability of open-source information and material, developments in biotechnology sciences, and inexpensive equipment make the production of bioweapons an attractive option for non-state actors. For example, in recent times individuals and non-state actors have developed or obtained ricin and anthrax with the intention of using it for either personal or political harm. Biological agents are not constrained by sovereign borders and can have a devastating effect either in the form of an infectious disease pandemic or as a result of scientific experimentation. This chapter analyses key issues and problems associated with biological security issues and dual-use research including governance arrangements to address those concerns.
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Border Inspection and Trade Diversion: Risk Reduction vs. Risk Substitution
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International trade increasingly brings previously separated geographical regions into contact with one another and increases the frequency of those contacts. These trends bring many benefits to the trading partners involved, but increasing international trade also facilitates the spread of pathogens and increases disease risks. The rapid growth of trade, transport, and travel across national borders has increased the frequency of introduction, establishment, and spread of invasive infectious pathogens (Jones et al. 2008). The development of new trade pathways and the growth in the number and volume of commodities traded increase the likelihood that novel infectious pathogens are introduced to importing or stop-over countries. The growth in trade volumes has increased the risk that introduced pathogens establish and spread, because it has increased the frequency with which infectious pathogens are introduced (Cassey et al. 2004; Dalmazzone 2000; Semmens et al. 2004). Other factors such as the bioclimatic similarities between trading partners, the vulnerability of ecosystems in the importing countries, and risk management policies adopted by both importing and exporting countries also influence the risks of invasive infectious pathogens (Wiens and Graham 2005).
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Porcine Epidemic Diarrhea
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Porcine epidemic diarrhea (PED) first appeared in England and Belgium in the 1970s. The etiological agent of the disease is porcine epidemic diarrhea virus (PEDV), which belongs to Coronaviridae. The disease has spread globally and became an endemic disease in many Asian and European countries causing transient diarrhea in postweaning pigs with low mortalities for several decades. Since late 2010, field outbreaks of PED, which reemerged in China, spread to Asian and some European countries and emerged in North America; all led to enormous economic losses in porcine industry. New variants of PEDV exhibit not only significant genetic variations as compared to historic PEDV strains but also more virulent causing severe vomiting and watery yellowish diarrhea in suckling piglets under 1 week of age. Factors underlying the potential pathogenesis of the recent PEDV outbreaks include the mutation of the virus, the lacking of maternal antibodies for the protection of piglets, and the slower turnover rate of enterocytes (5–7 days) of the neonatal piglets as compared to postweaning pigs (2–3 days). The emerging and reemerging of the new variants of PEDV highlight the importance of reviewing the etiology, pathogenesis, diagnosis, and epidemiology of the disease.
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The Process and Practice of Negotiation
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Global health diplomacy has been defined as the art and practice of negotiation in relation to global health issues. This chapter draws on generic concepts of negotiation as a process of diagnosis, formula development, exchange and implementation, reflecting the shared and sometimes contested values, power relationships and interests of the many different actors involved. It sets out a framework for understanding the main phases of global health negotiation process as they arise in many different contexts. The negotiation of global health issues is shown to be a driver of the regimes of global health governance institutions that are shaped by the new trends in global governance described in the previous chapter. The leadership and development of diplomatic negotiations at every level with an increasing range of actors is therefore key to global governance for health.
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Microbes, Transmission Routes and Survival Outside the Body
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Microbes like bacteria, virus, parasites and fungi may naturally colonize skin and mucous membranes without any sign of illness, for a longer or shorter period, in all humans, animals, fish, parasites, plants and all other living beings. Some types may be more invasive in human tissue than others. Many microbes are free-living in the environment—in water, soil and air and on equipment—as a part of the normal microbial flora on the Earth. Most of them are not dangerous and live in peaceful symbiosis with other living beings and may also be transferred between living species, from man to animal or man to plants and environment—and vice versa. New and old human pathogenic microbes are increasing all over the world. Some agents, like drug-resistant bacteria and highly pathogenic viruses, are more dangerous than others, and some microbes may cause chronic devastating diseases. Transmission routes depend on the robustness of the microbe in the environment, virulence, infectious dose, anatomical site in the body, etc. Pathogenic microbes are spread by contact, air, water, food, beverages, contaminated equipment and environment and are more seldom vector-borne, by insects or animals. The following chapter is focused on the most frequent pathogenic microbes, their preselected localization in the body, transmission routes and survival in the environment.
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Services Innovation: Decision Attributes, Innovation Enablers, and Innovation Drivers
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Innovation in the services area — especially in the electronic services (e-services) domain — can be characterized by six decision-oriented attributes: decision-driven, information-based, real-time, continuously-adaptive, customer-centric and computationally-intensive. These attributes constitute the decision informatics paradigm. In turn, decision informatics is supported by information and decision technologies and based on the disciplines of data fusion/analysis, decision modeling and systems engineering. Out of the nine major innovation enablers in the services area (i.e., decision informatics, software algorithms, automation, telecommunication, collaboration, standardization, customization, organization, and globalization), decision informatics is shown to be a necessary enabler. Furthermore, four innovation drivers (i.e., collaboration, customization, integration and adaptation) are identified; all four are directed at empowering the individual — that is, at recognizing that the individual can, respectively, contribute in a collaborative situation, receive customized or personalized attention, access an integrated system or process, and obtain adaptive real-time or just-in-time input. In addition to expanding on current innovations in services and experiences, white spaces are identified for possible future innovations; they include those that can mitigate the unforeseen consequences or abuses of earlier innovations, safeguard our rights to privacy, protect us from the always-on, interconnected world, provide us with an authoritative search engine, and generate a GDP metric that can adequately measure the growing knowledge economy, one driven by intangible ideas and services innovation.
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Nanomaterial Effects on Viral Infection
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The potential for environmental and occupational exposures of populations to nanomaterials (NMs) has fostered concerns of associated adverse health effects, with a particular emphasis on pulmonary injury and disease. Many studies have revealed that several types of NMs can evoke a variety of biological responses, such as pulmonary inflammation and oxidative stress, which contribute to allergy, fibrosis, and granuloma formation. Less attention has been paid to health effects that may result from exposure to NMs and additional stressors such as pathogens, with a particular focus on susceptibility to viral infection. This chapter will summarize the current body of literature related to NMs and viral exposures with a primary focus on immune modulation. A summary of the studies performed and major findings to date will be discussed, highlighting proposed molecular mechanisms behind NM-driven host susceptibility, challenges, limitations, and future research needs. Specific mechanisms discussed include direct interaction between NMs and biological molecules, activation of pattern recognition receptors (PRRs) and related signaling pathways, production of oxidative stress and mitochondrial dysfunction, inflammasome activation, and modulation of lipid signaling networks.
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Severe Influenza Infection: Pathogenesis, Diagnosis, Management and Future Therapy
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Climate Change and Geoecology of South and Southeast Asia: An Introduction
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Climate change is projected to impact human health in many ways including changes in water availability and quality, air quality and sanitation, availability and access to food and nutrition and transmission of vector-borne diseases. Environmental consequences of climate change, such as extreme heat waves, rising sea levels, changes in precipitation resulting in flooding and droughts, intense hurricanes (cyclones, typhoons) and degraded air quality, can affect directly and indirectly the physical, social and psychological health of humans. Climate change and human health have emerged as an important focus of research in the World Health Organization since 2008. However, the First International Conference on Health and Climate organised by the WHO in August 2014 in Geneva recognises the relevance of the impact of climate change on human health from a global-change and health perspective. This chapter also highlights policies of the United States, China and India towards GHG emission reduction and the successful climate agreement in Paris in December 2015.
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2 Aangeboren immuniteit en acute ontsteking
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Een van de belangrijkste functies van het immuunsysteem is het beschermen van ons lichaam tegen infecties. Om deze bescherming te kunnen realiseren, moet aan een aantal voorwaarden worden voldaan: 1) het immuunsysteem moet het pathogeen ter plaatse en liefst specifiek kunnen herkennen; 2) het immuunsysteem moet het pathogeen zo snel mogelijk onschadelijk maken en opruimen; en 3) het immuunsysteem moet een geheugen opbouwen, zodat hetzelfde pathogeen een volgende maal sneller en efficiënter geëlimineerd kan worden. Hoewel het derde aspect een speciale eigenschap is van de adaptieve immuniteit, is voor de eerste twee punten een nauwe samenwerking tussen de innate (aangeboren) en de adaptieve (verworven) immuniteit noodzakelijk. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1613-7_2) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.
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Viral Lower Respiratory Tract Infections
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Lower respiratory tract infections in children are often viral in origin. Unfortunately in this time of significant antimicrobial resistance of infectious organisms, especially bacteria, there is still a tendency for clinicians to manage a child who coughs with antibiotics. In addition, the World Health Organization (WHO) has defined “pneumonia” as a condition that only occurs in children who have “fast breathing or chest wall indrawing”. That would delineate upper respiratory tract infections from those in the lower airway. However, in addition to pneumonia another important entity exists in the lower respiratory tract that is almost always viral in origin. This condition is acute viral bronchiolitis. The concept of “acute lower respiratory tract infection” (ALRTI) has emerged and it is becoming increasing evident from a number of studies that the infectious base of both acute pneumonia (AP) and acute bronchiolitis in children has a mixed etiology of microorganisms. Therefore, whilst certain clinical phenotypes do not require antibiotics the actual microbial etiology is much less distinct.
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Modelling the Dynamics of Host-Parasite Interactions: Basic Principles
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Mathematical modelling is a valuable tool for the analysis of the infectious diseases spread. Dynamical models may help to represent and summarize available knowledge on transmission and disease evolution, to test assumptions and analyse scenarios, and to predict outcomes of the host-pathogen interactions. This chapter aims at introducing basic concepts and methods of epidemiological modelling, in order to provide a starting point for further developments. After positioning modelling in the process of disease investigation, we first present the main principles of model building and analysis, using simple biological and also mathematical systems. We then provide an overview of the methods that can be employed to describe more complex systems. Last, we illustrate how the modelling approach may help for different practical purposes, including evaluation of control strategies. A brief conclusion discusses the challenge of including genetic and molecular variability in epidemiological modelling.
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The ER in Replication of Positive-Strand RNA Viruses
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All eukaryotic positive-sense single-strand RNA viruses, (+)ssRNA, replicate their genome in associationwith membranes of host cells. The presence of a replicating virus frequently induces proliferationand rearrangement of the host membranes into various cytopathic structures, including invaginations, vesicles,spherules or membranous webs. Such structures are considered to be virus-induced organelles specializedin replication functions. Virtually all membranes are able to be rearranged to support replication. Thus,membranes from peroxisomes, endosomes, lysosomes, vacuoles, mitochondria, and chloroplasts are used for(+)ssRNA virus replication, but the endoplasmic reticulum (ER) is by far the preferred organelle. The specifictype of membrane system utilized in assembling the viral replication complex is strictly dependent on individualviruses and is likely to be genetically determined. The various molecular interactions that govern ER targetingof plant viruses highlight how viruses can exploit the diversity of interactions that occurs between proteinsand membrane or lipid structures.
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Influenza
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Influenza, briefly known as flu, is an acute respiratory infectious disease caused by influenza virus. It spreads via droplets, with strong infectivity. Its incident rate ranks first in legal infectious diseases, with occurrences of outbreaks or pandemics. Its clinical symptoms are characterized by acute onset of high fever, fatigue, systemic muscular soreness and pain, as well as mild respiratory tract symptoms. Influenza more commonly occurs in autumns and winters. Although it has a short disease course and is self-limited, it may be complicated by pneumonia and other serious complications in populations including the elderly, infants and young children, patients with cardiac or pulmonary diseases, patients with other chronic diseases, and patients with compromised immunity. In some serious cases, death may even occur.
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7,675 |
Microspheres for Drug Delivery
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With advances in biotechnology, genomics, and combinatorial chemistry, a wide variety of new, more potent and specific therapeutics are being created. Because of common problems such as low solubility, high potency, and/or poor stability of many of these new drugs, the means of drug delivery can impact efficacy and potential for commercialization as much as the nature of the drug itself. Thus, there is a corresponding need for safer and more effective methods and devices for drug delivery. Indeed, drug delivery systems—designed to provide a therapeutic agent in the needed amount, at the right time, to the proper location in the body, in a manner that optimizes efficacy, increases compliance and minimizes side effects—were responsible for $47 billion in sales in 2002, and the drug delivery market is expected to grow to $67 billion by 2006.
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7,676 |
Pharmacogenomics and Personalized Medicine for Infectious Diseases
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Humans have been plagued by the scourge of invasion by pathogens leading to infectious diseases from the time in memoriam and are still the cause of morbidity and mortality among millions of individuals. Trying to understand the disease mechanisms and finding the remedial measures have been the quest of humankind. The susceptibility to disease of an individual in a given population is determined by ones genetic buildup. Response to treatment and the disease prognosis also depends upon individual’s genetic predisposition. The environmental stress induces mutations and is leading to the emergence of ever-increasing more dreaded infectious pathogens, and now we are in the era of increasing antibiotic resistance that has thrown up a challenge to find new treatment regimes. Discoveries in the science of high-throughput sequencing and array technologies have shown new hope and are bringing a revolution in human health. The information gained from sequencing of both human and pathogen genomes is a way forward in deciphering host-pathogen interactions. Deciphering the pathogen virulence factors, host susceptibility genes, and the molecular programs involved in the pathogenesis of disease has paved the way for discovery of new molecular targets for drugs, diagnostic markers, and vaccines. The genomic diversity in the human population leads to differences in host responses to drugs and vaccines and is the cause of poor response to treatment as well as adverse reactions. The study of pharmacogenomics of infectious diseases is still at an early stage of development, and many intricacies of the host-pathogen interaction are yet to be understood in full measure. However, progress has been made over the decades of research in some of the important infectious diseases revealing how the host genetic polymorphisms of drug-metabolizing enzymes and transporters affect the bioavailability of the drugs which further determine the efficacy and toxicology of the drugs used for treatment. Further, the field of structural biology and chemistry has intertwined to give rise to medical structural genomics leading the way to the discovery of new drug targets against infectious diseases. This chapter explores how the advent of “omics” technologies is making a beginning in bringing about a change in the prevention, diagnosis, and treatments of the infectious diseases and hence paving way for personalized medicine.
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Smallpox as a Weapon for Bioterrorism
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7,678 |
Genetic Basis of Myocarditis: Myth or Reality?
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The genetic basis of myocarditis remains an intriguing concept, at least as long as the definition of myocarditis constitutes the definitive presence of myocardial inflammation sufficient to cause the observed ventricular dysfunction in the setting of cardiotropic infections. Autoimmune or immune-mediated myocardial inflammation constitutes a complex area of clinical interest, wherein numerous and not yet fully understood role of hereditary auto-inflammatory diseases can result in inflammation of the pericardium and myocardium. Finally, myocardial involvement in hereditary immunodeficiency diseases, cellular and humoral, is a possible trigger for infections which may complicate the diseases themselves. Whether the role of constitutional genetics can make the patient susceptible to myocardial inflammation remains yet to be explored.
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7,679 |
Lungengefäßerkrankungen
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Das Lungenödem ist charakterisiert durch eine vermehrte interstitielle und/oder alveoläre Flüssigkeitseinlagerung. Zugrunde liegt entweder eine Erhöhung des kapillären Filtrationsdrucks, die zumeist kardial verursacht ist, oder eine erhöhte Durchlässigkeit der pulmonalen Gefäßschranke (⊡ Tab. 9.1).
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7,680 |
Protecting Information with Cybersecurity
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Virtually every system today confronts the cybersecurity threat, and the system architect must have the ability to integrate security features and functions as integral elements of a system. In this chapter, we survey this large, complex, and rapidly evolving subject with the goal of giving the reader a level of understanding that will enable incorporation of cybersecurity within an MBSE process and effective interaction with security experts. We begin by introducing the subject and describing the primary aspects of the current cybersecurity environment. We define fundamental terminology and concepts used in the cybersecurity community, and we describe the basic steps to include cybersecurity risk in an overall risk management process, which is a central SE responsibility. We then list some of the primary sources of information, guidance, and standards upon which a systems engineer can and should draw. Next, we summarize the major aspects of incorporating security controls in a system architecture and design to achieve an acceptable level of security risk for a system. We extend this to the increasingly important world of service-oriented, network-based, and distributed systems. We conclude with a brief presentation of the application of MBSAP to the specific issues of cybersecurity and summarize the characteristics of a Secure Software Development Life Cycle aimed at creating software with minimum flaws and vulnerabilities. We illustrate the application of cybersecurity principles and practices using the Smart Microgrid example. Chapter Objective: the reader will be able to apply the MBSAP methodology to systems and enterprises that require protection of sensitive data and processes against the growing cybersecurity threat and to work effectively with cybersecurity specialists to achieve effective secure system solutions.
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7,681 |
Infectious Diseases: The Role of the Healthcare Professional
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For the healthcare professional dealing with infections presents two main problems. First, managing detainees or police personnel who have contracted a disease and may be infectious or unwell, and second, handling complainants of assault, including police officers, who have potentially been exposed to an infectious disease. This chapter addresses some general principles of infection control and safety in the working environment and then goes on to discuss some infections that may be encountered in police custody and how they can best be managed.
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7,682 |
Part 3: Practical Implementation of Data Protection Environment
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A wide range of cloud related professionals (both legal and technical) in California have been interviewed regarding their experience with data protection and in particular the effects of the EU law on their business operations and the industry in general. Hereinafter, the results of these interviews will be analyzed and key issues addressed with a special focus on the new EU General Data Protection Regulation (GDPR).
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7,683 |
An Introduction to Networks in Epidemic Modeling
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We use a stochastic branching process to describe the beginning of a disease outbreak. Unlike compartmental models, if the basic reproduction number is greater than one there may be a minor outbreak or a major epidemic with a probability depending on the nature of the contact network. We use a network approach to determine the distribution of outbreak and epidemic sizes.
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Reticular Diseases
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Cases 27–65
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A 73-year-old Caucasian woman presented with hematemesis. She had been diagnosed with cryptogenic cirrhosis several years previously but her disease was well compensated. She was seen at a local hospital and underwent esophagogastroduodenoscopy (EGD) that demonstrated no signs of esophageal varices but a large mass in the fundus and some nodular changes in the stomach. The concern was for a gastric malignancy. She is transfused and sent to you for further investigation.
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7,686 |
Mosquitoes as Arbovirus Vectors: From Species Identification to Vector Competence
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Mosquitoes and other arthropods transmit a large number of medically important pathogens, in particular viruses. These arthropod-borne viruses (arboviruses) include a wide variety of RNA viruses belonging to the Flaviviridae family (West Nile virus (WNV), Usutu virus (USUV), Dengue virus (DENV), Japanese encephalitis virus (JEV), Zika virus (ZIKV)), the Togaviridae family (Chikungunya virus (CHIKV)), and Bunyavirales order (Rift Valley fever virus 1. Who could contribute to such an outbreak? Information about mosquito species resident or imported, potential hosts and viruses able to infect vectors and hosts in Germany is needed. 2. Where would competent mosquito species meet favorable conditions for transmission? Information on the minimum requirements for efficient replication of the virus in a given vector species and subsequent transmission is needed. 3. How do viruses and vectors interact to facilitate transmission? Information on the vector immunity, vector physiology, vector genetics, and vector microbiomes is needed.
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Trends and Perspectives
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Throughout the book chapters, researchers have highlighted the recent advancement in microfluidic areas, particularly those involving microdroplets.
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7,688 |
Diagnosis of Tuberculosis: Nanodiagnostics Approaches
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Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide. The burden of TB is alarmingly high in developing countries, where diagnosis latent TB infection (LTBI), Extra-pulmonary tuberculosis (EPTB), drug-resistant tuberculosis (DR-TB), HIV-associated TB, and paediatric TB is still a challenge. This is mainly due to delayed or misdiagnosis of TB, which continues to fuel its worldwide epidemic. The ideal diagnostic test is still unavailable, and conventional methods remain a necessity for TB diagnosis, though with poor diagnostic ability. The nanoparticles have shown potential for the improvement of drug delivery, reducing treatment frequency and diagnosis of various diseases. The engineering of antigens/antibody nanocarriers represents an exciting front in the field of diagnostics, potentially flagging the way toward development of better diagnostics for TB. This chapter discusses the presently available tests for TB diagnostics and also highlights the recent advancement in the nanotechnology-based detection tests for M. tuberculosis.
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SARS
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Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China.
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7,690 |
Histopathology in Coronavirus-Induced Demyelination
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The experimental model system of coronavirus mouse hepatitis virus (MHV) induced demyelination in 4–6 week old C57Bl/6 or Balb/c mice exhibits a biphasic disease and two distinct forms of virus-induced demyelination. During the acute phase of the disease MHV infection causes acute encephalitis, and some strains of virus cause also hepatitis. Infection with the JHM strain of MHV causes severe panencephalitis, whereas MHV-A59 causes mild to moderate encephalitis involving specific limbic and limbic related areas of the brain and brain stem. The target cells are neurons and glia including oligodendrocytes. Demyelination during the acute stage is due to cytolytic infection of oligodendrocytes. After two weeks, the disease process enters a chronic stage of immune-mediated demyelination, in the presence of high levels of anti-viral antibodies and persistent low levels viral RNA in glial cells, without detectable levels of infectious virus or viral antigens.
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7,691 |
SOARS: Spot Oriented Agent Role Simulator — Design and Implementation
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In this paper we present the design of an agent-based simulation language called SOARS (Spot Oriented Agent Role Simulator). SOARS is designed to describe agent activities according to roles within social and organizational structures. Role taking processes can be described in our language. SOARS is also designed according to the theory of agent-based dynamic systems. Decomposition of multi-agent interaction is one of the most important characteristics of our framework. The notion of spot and stage gives spacial and temporal decomposition of interaction among agents. We apply our multi-agent framework to policy analysis of emerging virus protection in the case of SARS. In the latter part of the paper, we explain the implementation of the SOARS simulation platform. The simulation engine and related built-in functional objects are implemented in Java language. An application user can describe the agent-based simulation model only by writing script in SOARS script language without knowledge of Java classes. If needed, the user can customize the function of SOARS by implementing additional Java classes. The easiest way to customize is to develop special functional objects, and the SOARS platform will be the interface between such customized objects.
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7,692 |
Disaster Perceptions
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Generally speaking, perception includes individuals’ subjectivity in terms of how they see or assess the characteristics of a phenomenon. Risk perception is vital to understanding what risks people consider to be acceptable, and what risk reduction programs have a better chance of being accepted. Risk perception is influenced by a variety of factors including the kind of information available and how that information is processed; the personality and emotional state of the perceiver; their personal experiences and prejudices; and socio-economic factors, to name but a few. Risk perception, risk tolerance, and high or low risk-taking behaviors are all interconnected. The nature and consequences of a potential threat, as well as its proximity, also contribute to how it is perceived by society. In this era of social media, the media is vital to ensuring that disaster news is covered more objectively. This chapter includes survey-based studies conducted in Canada as powerful testimonies to the importance of risk perception among various groups, including average citizens and emergency managers.
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7,693 |
Infestationen und Infektionen bei Migranten – Die wichtigsten Erkrankungen
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Skabies (Krätze) ist bei Migranten sehr häufig. Über den Gängen der Krätzmilbe ist die Haut entzündlich verändert. An Händen und Füssen sind die Veränderungen vor allem in den interdigitalen Räumen erkennbar. Kopfläuse nehmen als Problem zu. Sie sind nur am menschlichen Kopf überlebensfähig. Flohstiche entstehen auch an bedeckten Körperstellen. An der Stichstelle entwickelt sich eine stark juckende Quaddel mit einer zentralen Blutung. Die Bettwanze sticht in der Nacht und saugt Blut. Stiche sind typischerweise longitudinal angeordnet. Unter den Parasiten haben Würmer eine große Bedeutung. Bei Kindern in Deutschland kommen Madenwürmer (Oxyuren) am häufigsten vor. Wurmeier werden anal, perianal und auch vaginal abgelegt und führen zu einem starken nächtlichen analen Pruritus. Unter den Infektionen hat die Tuberkulose bei Migranten eine höhere Prävalenz als in Deutschland gewohnt. Unter den Migranten aus dem subsaharischen Afrika ist auf das Vorliegen von HIV-Infektionen zu achten.
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7,694 |
Fibrous Layer Filter
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Granular layer, fibrous layer, microporous membrane, membrane covered fibrous layer, screen mesh and perforated plate can be used to remove particles, which are classified as barrier-type filter.
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7,695 |
Public Health Law and Biological Terrorism
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7,696 |
Case Study: The continuous realization of growth synergies
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Following the single cause study approach for investigating our empirical research question, this chapter presents an in-depth case report of the continuous realization of growth synergies at our research site ElectroCorp. It provides the context and basis for our interference of constructs and propositions in the next chapter.
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7,697 |
Pediatric Interstitial (Diffuse) Lung Disease
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Interstitial (diffuse) lung diseases in infants and children comprise a rare heterogeneous group of parenchymal lung disorders, with clinical syndromes characterized by dyspnea, tachypnea, crackles, and hypoxemia. They arise from a wide spectrum of developmental, genetic, inflammatory, infectious, and reactive disorders. In the past, there has been a paucity of information and limited understanding regarding their pathogenesis, natural history, imaging findings, and histopathologic features, which often resulted in enormous diagnostic challenges and confusion. In recent years, there has been a substantial improvement in the understanding of interstitial lung disease in pediatric patients due to the development of a structured classification system based on the etiology of the lung disease, established pathologic criteria for consistent diagnosis, and the improvement of thoracoscopic techniques for lung biopsy. Imaging plays an important role in evaluating interstitial lung diseases in infants and children by confirming and characterizing the disorder, generating differential diagnoses, and providing localization for lung biopsy for pathological diagnosis. In this chapter, the authors present the epidemiology, challenges, and uncertainties of diagnosis and amplify a recently developed classification system for interstitial lung disease in infants and children with clinical, imaging, and pathological correlation.
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7,698 |
Measles
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Measles is an acute respiratory infectious disease caused by measles virus. Clinically, it is characterized by fever, rhinorrhea, conjunctival congestion, respiratory catarrh symptoms, oral mucosa spots, and red skin maculopapules. The patients with acute measles are the only source of its infection, who are infectious from the final 1–2 days of the incubation period to the day 5 after skin rash. Measles is commonly transmitted via respiratory droplets, with occurrence all year round but more commonly in winters and springs. Measles is the most common infectious disease in children, with strong infectivity. In recent years, the cases of measles in adults are increasing. Elimination of measles has been listed as the next objective of WHO after elimination of poliomyelitis.
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7,699 |
Virus-like Particle Vaccines for Norovirus Gastroenteritis
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Gastroenteritis (GE) and its associated diarrheal diseases remain as one of the top causes of death in the world. Noroviruses (NoVs) are a group of genetically diverse RNA viruses that cause the great majority of nonbacterial gastroenteritis in humans. However, there is still no vaccine licensed for human use to prevent NoV GE. The lack of a tissue culture system and a small animal model further hinders the development of NoV vaccines. Virus-like particles (VLPs) that mimic the antigenic architecture of authentic virions, however, can be produced in insect, mammalian, and plant cells by the expression of the capsid protein. The particulate nature and high-density presentation of viral structure proteins on their surface render VLPs as a premier vaccine platform with superior safety, immunogenicity, and manufacturability. Therefore, this chapter focuses on the development of effective NoV vaccines based on VLPs of capsid proteins. The expression and structure of NoV VLPs, especially VLPs of Norwalk virus, the prototype NoV, are extensively discussed. The ability of NoV VLPs in stimulating a potent systemic and mucosal anti-NoV immunity through oral and intranasal delivery in mice is presented. The advantages of plant expression systems as a novel production platform for VLP-based NoV vaccines are discussed in light of their cost-effectiveness, production speed, and scalability. Recent achievements from the first successful demonstration of NoV VLP production in plant expression system under the current Good Manufacture Practice (cGMP) regulation by the US Food and Drug Administration (FDA) are detailed. Moreover, results of human clinical trials demonstrating the safety and efficacy of insect and plant-derived NoV VLPs are also presented. Due to the diversity of capsid protein among different NoV strains and its rapid antigenic drift, we speculate that vaccine development should focus on multivalent VLP vaccines derived from capsid proteins of the most prevalent strains. With the very recent approval of the first plant-made biologics by the FDA, we also speculate that plant-based production systems will play an important role in manufacturing such multivalent VLP-based NoV vaccines.
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