title: Single-Particle cryo-EM as a Pipeline for Obtaining Atomic Resolution Structures of Druggable Targets in Preclinical Structure-Based Drug Design

text: Single-particle cryo-electron microscopy (cryo-EM) and three-dimensional (3D) image processing have gained importance in the last few years to obtain atomic structures of drug targets. Obtaining atomic-resolution 3D structure better than ~2.5 Å is a standard approach in pharma companies to design and optimize therapeutic compounds against drug targets like proteins. Protein crystallography is the main technique in solving the structures of drug targets at atomic resolution. However, this technique requires protein crystals which in turn is a major bottleneck. It was not possible to obtain the structure of proteins better than 2.5 Å resolution by any other methods apart from protein crystallography until 2015. Recent advances in single-particle cryo-EM and 3D image processing have led to a resolution revolution in the field of structural biology that has led to high-resolution protein structures, thus breaking the cryo-EM resolution barriers to facilitate drug discovery. There are 24 structures solved by single-particle cryo-EM with resolution 2.5 Å or better in the EMDataBank (EMDB) till date. Among these, five cryo-EM 3D reconstructions of proteins in the EMDB have their associated coordinates deposited in Protein Data Bank (PDB), with bound inhibitor/ ligand. Thus, for the first time, single-particle cryo-EM was included in the structure-based drug design (SBDD) pipeline for solving protein structures independently or where crystallography has failed to crystallize the protein. Further, this technique can be complementary and supplementary to protein crystallography field in solving 3D structures. Thus, single-particle cryo-EM can become a standard approach in pharmaceutical industry in the design, validation, and optimization of therapeutic compounds targeting therapeutically important protein molecules during preclinical drug discovery research. The present chapter will describe briefly the history and the principles of single-particle cryo-EM and 3D image processing to obtain atomic-resolution structure of proteins and their complex with their drug targets/ligands.


title: 2 Infecties van de bovenste luchtwegen

text: 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.


title: Biosafety and Bioethics

text: The advancement in technology is likely to tame several life forms present on earth. Microorganisms are posing a big challenge due to difficulties encountered to control the diseases caused by them. Working with deadly disease-causing microorganisms for their characterization, diagnostics or therapeutics and vaccine development purposes are posing increasingly potential biosafety problems for laboratory workers. Thus, an appropriate biosafe working environment may protect workers from laboratory-induced infections. Biotechnology has the ability to solve the upcoming problems of the world’s increasing population. However, there is often reluctance among the public to accept and support biotechnological products in medicine, industry, or agriculture. There are many safety and ethical issues raised for GM crops and human cloning. Raising transgenic animals and plants has fueled ethical concerns, and the scientists have faced a lot of resistance where genetically modified crop plants or reproductive cloning research of human beings is involved. Thus, biosafety and bioethics are continuously being expanded to combine the rationale of ever-increasing scientific knowledge in biotechnology that is often in conflict with the long-standing social and moral value system of our society.


title: 7 Hoesten, van symptoom tot diagnose

text: Hoesten behoort, naast klachten van het houdings- en bewegingsapparaat, tot de twee belangrijkste contactredenen voor consultatie van de huisarts. De hoogste incidentie- en prevalentiecijfers voor hoesten worden gevonden in de leeftijdsgroep van 0-4 jaar (respectievelijk 81,2 en 82,4).


title: Broncopneumopatia cronica ostruttiva (BPCO)

text: La broncopneumopatia cronica ostruttiva (BPCO) è una delle maggiori cause di morbilità e mortalità in tutto il mondo. A causa dell’elevata prevalenza e della possibilità di essere una patologia altamente invalidante, i costi della BPCO possono rappresentare un importante impegno economico e sociale per la spesa sanitaria.


title: Alpha-1 Antitrypsin as a Therapeutic Agent for Conditions not Associated with Alpha-1 Antitrypsin Deficiency

text: Alpha-1 antitrypsin is a positive acute phase reactant whose serum level rises in response to inflammatory stress, presumably to balance pro-inflammatory processes. In addition to its serine protease inhibitory action, alpha-1 antitrypsin exhibits broader anti-inflammatory and immunomodulatory activity, and increasing its serum concentration by the administration of exogenous alpha-1 antitrypsin to above-normal levels potentially could be therapeutic in conditions other than alpha-1 antitrypsin deficiency. In vitro observations, studies in animal models and in some instances early human trials suggest that intravenous or inhaled alpha-1 antitrypsin has beneficial effects in type 1 diabetes, viral infections, graft-versus-host disease, cystic fibrosis, and alpha-1 antitrypsin-replete chronic obstructive pulmonary disease among others. While the results of pivotal clinical trials have not been reported to date, new indications for alpha-1 antitrypsin therapy are likely to emerge in the future based on currently available scientific data.


title: Enhancement of Medicinally Important Bioactive Compounds in Hairy Root Cultures of Glycyrrhiza, Rauwolfia, and Solanum Through In Vitro Stress Application

text: Enhancement of secondary metabolites through elicitation in hairy root culture is a very effective method which is broadly used to simulate the stress responses in plants. Elicitors are compounds that induce plants to produce secondary metabolites at elevated levels and reduce the processing time required to achieve high product concentrations. Hairy root cultures are considered as an excellent alternative for the supply of pharmaceutically important secondary metabolites/bioactives, due to their inherent genetic and biochemical stability. Plant-based secondary metabolites are well accepted in India as well as other countries to cure even the serious medical problems. In this chapter, three medicinally important plants are discussed in which stress-based elicitation of secondary metabolites has been achieved in hairy root cultures. These three plants contain important secondary metabolites in their different parts. Glycyrrhizin found in Glycyrrhiza glabra plant is used as antiulcer, immunomodulatory, antiallergic, and anti-inflammatory. Glycyrrhizin is also effective against HIV and severe acute respiratory syndrome (SARS)-like viruses. In Solanum plant, steroidal glycoalkaloids contain pharmaceutically important secondary metabolites. Solasodine, a major alkaloid of Solanum plant, is used as a contraceptive in different parts of the world. Ajmaline and ajmalicine are important root-specific indole alkaloids of Rauwolfia serpentina. Ajmalicine is useful in circulatory disorders, while ajmaline is principally known for its antiarrhythmic and antihypertensive activities. The main objective of this chapter is to provide knowledge in these plants regarding elicitation-based enhancement of valuable secondary metabolites in the form of research studies conducted till date (as per author’s knowledge).


title: Acronimi e abbreviazioni in chirurgia e in medicina

text: “The patient went from the ER to the OR and then to the ICU”. Indubbiamente il lessico dei medici è ricco di abbreviazioni, tanto che gli operatori della sanità in generale e i chirurghi in particolare adoperano perlomeno dieci abbreviazioni per minuto (questa è una statistica fatta in casa, non citatela).


docid: fxajghna

title: Rituximab

text: Rituximab (Rituxan(®), MabThera(®), and Genentech/Roche) is a chimeric murine/human monoclonal IgG1k antibody directed against the CD20 antigen located at the surface of normal and malignant B lymphocytes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/978-88-470-5313-7_35) contains supplementary material, which is available to authorized users.


docid: mludwtgc

title: Endodontics in Systemically Compromised Patients

text: A substantial number of people in today’s world are elderly and as the incidence of a number of pathologies increases with age, it is predicted to produce millions of individuals with systemic medical conditions that can affect oral health and subsequent dental treatment. The dental management of these medically compromised patients can be sometimes problematic in terms of oral complications, dental therapy, and emergency care. One of the challenges faced by dental specialists today is the assessment and management of these patients. As mentioned in detail in Chap. 12, geriatric patients are much more likely to be at least partially dentulous having a complex medical history and the use of multiple medications.


title: Social Communications Assisted Epidemic Disease Influence Minimization

text: This work explores the use of social communications for epidemic disease control. Since the most infectious diseases spread through human contacts, we focus on modeling the diffusion of diseases by analyzing the social relationship among individuals. In other words, we try to capture the interaction pattern among human beings using the social contact information, and investigate its impact on the spread of diseases. Particularly, we investigate the problem of minimizing the expected number of infected persons by treating a small fraction of the population with vaccines. We prove that this problem is NP-hard, and propose an approximate algorithm representing a preventive disease control strategy based on the social patterns. Simulation results confirm the superiority of our strategy over existing ones.


Building on Experience: Learning Lessons from Past Framework Programmes


title: Infectieziekten

text: De bespreking van ziektebeelden in dit boek wordt begonnen met infectieziekten, niet zozeer omdat deze een van de belangrijkste categorieën in de huisartspraktijk zouden vormen, maar omdat alle classificatiesystemen van ziekten hiermee beginnen. Op de keper beschouwd bieden de classificatiesystemen onder het hoofdstuk infectieziekten een restgroep van ziekten omdat een aantal infecties niet hier, maar bij orgaansystemen is ondergebracht. Luchtweginfecties bijvoorbeeld, die zo’n groot deel van het werk van de huisarts uitmaken, worden onder de tractus respiratorius geregistreerd (en in dit boek in hoofdstuk 8 besproken). Soms worden nieuwe infectieziekten aan het hoofdstuk infectieziekten toegevoegd (zoals hiv-infectie). Het bekend worden van de rol van een micro-organisme in de etiologie van een aandoening leidt overigens niet altijd tot aanpassingen (bijvoorbeeld Helicobacter pylori-infectie bij ulcus duodeni en ulcus ventriculi).


title: Il lavaggio broncoalveolare (BAL) in età pediatrica

text: Il lavaggio broncoalveolare o BAL, permettendo di ottenere le cellule ed i soluti presenti sulla superficie epiteliale del tratto respiratorio distale, si è dimostrato una metodica di ricerca essenziale per lo studio dei meccanismi eziopatogenetici delle malattie del polmone profondo, come ad esempio lo studio delle interstiziopatie, su cui esiste una vastissima letteratura di dati ottenuti con il BAL. Oltre a questo aspetto di metodica di ricerca, il BAL rappresenta perè anche una procedura diagnostica insostituibile nella pratica clinica quotidiana.


title: Fungal Vaccines and Vaccination: Problems and Perspectives

text: Vaccines against human pathogenic fungi, a rather neglected medical need until few years ago, are now gaining steps in the public health priority scale. The awareness of the rising medical threat represented by the opportunistic fungal infections among the health care-associated infections, the advances in the knowledge of fungal pathogenicity and immune response and the extraordinary progress of biotechnology have generated enthusiasm and critical new tools for active and passive anti-fungal vaccination. The discovery that antibodies play a critical role for protection against fungal infection has greatly contributed to the advancements in this field, in recognition that almost all useful vaccines against viral and bacterial pathogens owe their protective efficacy to neutralizing, opsonizing or otherwise effective antibodies. Overall, there is more hope now than few years ago about the chances of generating and having approved by the regulatory authorities one or more antifungal vaccines, be active or passive, for use in humans in the next few years. In particular, the possibility of protecting against multiple opportunistic mycoses in immuno-depressed subjects with a single, well-defined glucan-conjugate vaccine eliciting directly anti-fungal antibodies may be an important step to achieve this public health goal


title: Analyzing Global Epidemiology of Diseases Using Human-in-the-Loop Bio-Simulations

text: Humanity is facing an increasing number of highly virulent and communicable diseases such as influenza. Combating such global diseases requires in-depth knowledge of their epidemiology. The only practical method for discovering global epidemiological knowledge and identifying prophylactic strategies is simulation. However, several interrelated factors, including increasing model complexity, stochastic nature of diseases, and short analysis timeframes render exhaustive analysis an infeasible task. An effective approach to alleviate the aforementioned issues and enable efficient epidemiological analysis is to manually steer bio-simulations to scenarios of interest. Selective steering preserves causality, inter-dependencies, and stochastic characteristics in the model better than “seeding”, i.e., manually setting simulation state. Accordingly, we have developed a novel Eco-modeling and bio-simulation environment called SEARUMS. The bio-simulation infrastructure of SEARUMS permits a human-in-the-loop to steer the simulation to scenarios of interest so that epidemics can be effectively modeled and analyzed. This article discusses mathematical principles underlying SEARUMS along with its software architecture and design. In addition, the article also presents the bio-simulations and multi-faceted case studies conducted using SEARUMS to elucidate its ability to forecast timelines, epicenters, and socio-economic impacts of epidemics. Currently, the primary emphasis of SEARUMS is to ease global epidemiological analysis of avian influenza. However, the methodology is sufficiently generic and it can be adapted for other epidemiological analysis required to effectively combat various diseases.


title: Lungenversagen

text: Das akute Lungenversagen ist eine schwere diffuse entzündliche Erkrankung der Lunge. Nach der „American-European Consensus Conference“ (Bernard et al., 1994) wird zwischen einem ARDS — acute respiratory distress syndrom und einem ALI — acute lung injury unterschieden.


docid: eoxzzhdd

title: Dangerous Viral Pathogens of Animal Origin: Risk and Biosecurity: Zoonotic Select Agents

text: Most of emerging infectious diseases affecting humans are of animal origin and transmitted under natural circumstances from either, wild or domestic vertebrate animals giving the way of zoonotic infection or epidemics. Zoonotic diseases carry a common ancient history between human and animals as a result of pathogen exchanges involving transgression of the species barrier. Nowadays, several agents have been targeted for their potential to be a major risk for human and animal populations and, have been characterized by their potential to be highly pathogenic and/or transmissible, and lacking of any means of protection. Those agents have been listed as “Select Agents” having the potential to pose a severe threat to both human and animal health, as well as to animal and plant products. Several of the most dangerous agents responsible of viral hemorrhagic fever are review in this chapter including: Ebola virus, Marburg virus, Rift valley fever virus, Kyasanur forest virus, Omsk hemorrhagic fever virus, Alkhurma hemorrhagic fever virus.


title: Concerns and Threats of Contamination on Aquatic Ecosystems

text: Aquatic ecosystems are the ultimate sinks for the contaminants. Water contamination is the outcome of human activities such as urbanization, industrialization, and agricultural activities. The overuse of pesticides and fertilizers and sewage from residential and industrial areas ultimately find its way to aquatic environment. Thus results in the degradation of the water quality and leads to the spread of infectious diseases such as dysentery, diarrhea, and jaundice. Contamination in aquatic environs is one of the leading types of pollution which has significant negative health issues and mortality. Water has a natural capacity to neutralize the contamination, but when contamination becomes uncontrolled, water will lose its self-generating capacity. Therefore, there is a need for regular monitoring and controlling of pollutant discharge into the nearby aquatic environs.


title: Die Diagnose der Sepsis

text: Die frühe Diagnostik der Sepsis ist das Nadelöhr für die weitere Senkung der Sepsissterblichkeit. Inzwischen liegen Befunde vor, dass, vergleichbar mit akutem Myokardinfarkt und Schlaganfall, dem Faktor Zeit eine wichtige Rolle zukommt. Demgegenüber gibt es keine allgemein akzeptierte Sepsisdiagnostik, die der Forderung nach früher Diagnose und der Unabhängigkeit vom Erfahrungsstand des jeweiligen Arztes Rechnung tragen könnte.


docid: gjnyfzmo

title: 14 Neusverstopping

text: Acute neusverstopping is een frequente aandoening. Meestal is het geen geïsoleerd symptoom, maar treedt zij gecombineerd op met andere klachten van de neus. In overgrote meerderheid is de oorzaak een virale infectie die vanzelf overgaat, en heeft verdere diagnostiek geen consequenties voor de therapie. Bij chronische klachten is verdere diagnostiek wel zinvol; een allergie of hyperreactiviteit is het meest waarschijnlijk. Bij chronische neusverstopping is aandacht voor chronisch gebruik van decongestieve neusdruppels van belang. Persisterende eenzijdige neusverstopping, zeker wanneer dit gepaard gaat met bloederige afscheiding, is een alarmsymptoom.


title: An Overview of Antimicrobial Properties of Different Classes of Phytochemicals

text: Plants produce a great diversity of phytochemicals, the beneficial properties of which have been used by humans for centuries since the advent of human civilization. With the discovery of effective and potent antimicrobial compounds, these synthetic antimicrobial compounds are widely used to prevent and cure microbial diseases. However, the development of antibiotic resistant strains of bacteria, reduced efficacy and safety of antimicrobials and the search of new antimicrobials against emerging incurable diseases by conventional antimicrobial agents have revived to explore phytochemicals as an alternative to synthetic antimicrobial compounds. Although numerous studies have been conducted in vitro and in vivo in the recent years on the efficacy of plant phytochemicals as antimicrobial agents, this chapter provides an overview of the antimicrobial properties of some major group of phytochemicals, namely, different phenolic compounds, alkaloids, saponins, iridoids and secoiridoids, polyacetylenes, glucosinolates, terpenoids, sulfinate, limonoids (tetranortepenoids) and anthranoids against pathogenic bacteria, fungi, viruses and commensal bacteria in the intestinal tracts of humans and animals. This chapter also discusses their antimicrobial mechanisms of action, the efficiency of different groups of phytochemicals against multiple-drug resistant bacteria, the effect of active dietary phytometabolites on the beneficial and pathogenic microbes of the gastrointestinal tracts and the outcomes of combination of phytofactors and drugs interactions.


title: Disruption of the Blood-Brain Barrier During Neuroinflammatory and Neuroinfectious Diseases

text: As the organ of highest metabolic demand, utilizing over 25% of total body glucose utilization via an enormous vasculature with one capillary every 73 μm, the brain evolves a barrier at the capillary and postcapillary venules to prevent toxicity during serum fluctuations in metabolites and hormones, to limit brain swelling during inflammation, and to prevent pathogen invasion. Understanding of neuroprotective barriers has since evolved to incorporate the neurovascular unit (NVU), the blood-cerebrospinal fluid (CSF) barrier, and the presence of CNS lymphatics that allow leukocyte egress. Identification of the cellular and molecular participants in BBB function at the NVU has allowed detailed analyses of mechanisms that contribute to BBB dysfunction in various disease states, which include both autoimmune and infectious etiologies. This chapter will introduce some of the cellular and molecular components that promote barrier function but may be manipulated by inflammatory mediators or pathogens during neuroinflammation or neuroinfectious diseases.


title: Identifying Major Histocompatibility Complex Supertypes

text: Human leukocyte antigen (HLA) recognizes antigenic fragments and presents them to T cells. HLA is polymorphic. There are over 2000 different HLA alleles at present and the number is constantly increasing. However, antigen binding studies are limited to a small proportion of these alleles; the binding specificities of most alleles are unknown. Several research groups have attempted to partition different HLA alleles into groups. In this chapter previous classifications are reviewed and we present two chemometric approaches to classifying class I HLA alleles. The program GRID is used to calculate interaction energy between protein molecules and defined chemical probes. These interaction energy values are imported into another program GOLPE and used for principal component analysis (PCA) calculation, which groups HLA alleles into supertypes. Amino acids that are involved in the classification are displayed in the loading plots of the PCA model. Another method, hierarchical clustering based on comparative molecular similarity indices (CoMSIA) is also applied to classify HLA alleles and the results are compared with those of the PCA models.


Anhang


docid: wqqbqbtf

title: Hemophagocytic Lymphohistiocytosis Syndromes

text: Hemophagocytic lymphohistiocytosis (HLH) is a non-malignant, life-threatening hyperinflammatory condition resulting from dysregulation of normal innate and adaptive immune responses. Defects in immune effector cell cytotoxic mechanisms have been identified in many HLH syndromes. Infants and children most often present with this condition, but new onset disease may be observed in adults as well. Presenting signs and symptoms include the classic triad of fever, hepatosplenomegaly, and cytopenias, but neurologic impairment, respiratory and cardiovascular embarrassment, liver disease with coagulopathy, diarrhea, and rash may feature prominently. Diagnosis relies upon fulfilling clinical criteria and laboratory assessments including serum ferritin, soluble IL-2 receptor levels, and natural killer (NK) cell function studies. Treatment consists of excellent supportive care for the critically ill. Specific disease modifying therapy employs immunosuppressant medications and often hematopoietic stem cell transplant. HLH syndromes are frequently fatal if untreated. With current interventions survival ranges 60–70 %.


title: Dependability and Security in Medical Information System

text: Medical Information Systems (MIS) help medical practice and health care significantly. Security and dependability are two increasingly important factors for MIS nowadays. In one hand, people would be willing to step into the MIS age only when their privacy and integrity can be protected and guaranteed with MIS systems. On the other hand, only secure and reliable MIS systems would provide safe and solid medical and health care service to people. In this paper, we discuss some new security and reliability technologies which are necessary for and can be integrated with existing MISs and make the systems highly secure and dependable. We also present an implemented Middleware architecture which has been integrated with the existing VISTA/CPRS system in the U.S. Department of Veterans Affairs seamlessly and transparently.


title: Microbial Forensics: Beyond a Fascination

text: Microbiology has seen a great transition from culture-based identification of microbes using various biochemical and microscopic observations to identify and functionally characterize the microbes by just collecting the DNA and sequencing it. This advancement has not only moved in and around microbiology but has found its applications in fields which were earlier considered to be the remote ones. Forensics is one such field, where tracing the leftover evidence on a crime scene can lead to the identification and prosecution of the culprit. When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—“microbial forensics.” Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Studies have supported the assumption that skin or surface microflora of an individual is somewhat related with the microflora found on the objects used by that individual and efforts are ongoing to see if this is found consistently in various surroundings and with different individuals. Once established, this technique would facilitate accurate identification and differentiation of an individual or suspect to guide investigations along with conventional evidence. Legal investigations are not only the field where microbial forensic could help. Agriculture, defense, public health, tourism, etc. are the fields wherein microbial forensics with different names based on the fields are helping out and have potential to further support other fields.


title: Exons and Introns

text: Organisms can he divided into those whose cells do not have a nucleus, the single celled “prckaryotes” (Greek: pro = before; karyon = nucleus), and those whose cells have a nucleus, the single- or multi-celled “eukaryotes” (Greek: eu = good or normal; karyon = nucleus). Prokaryotes include species of bacteria (eubacteria) and archaea (archaebacteria), the latter being a bacteria- like group sometimes found in extreme environments (e.g. hot springs). Eukaryotes (eukarya) include all species of animals and plants, hoth singlecelled (protozoa, protophyta) and multi-celled (metazoa, metaphyta).


title: Protection of Upper Respiratory Tract, Mouth and Eyes

text: Pathogenic bacteria and viruses may invade via upper and lower respiratory tract and via eye mucosa. When an infected person coughs or sneezes heavily, small, invisible droplets with the infective agent may reach a good distance from the source. By using the right form of protection at the right time, infection and disease are prevented. The present chapter is focused on the protection against airborne infections.


title: The Clinical Definitions of Asthma

text: It is believed that the term “asthma” was coined by Hippocrates around 450 bc. The term literally means “panting,” from the Greek. Descriptions of the clinical presentation of those affected with asthma appear in medical literature throughout history.


title: What the Intensivists Need to Know About Critically Ill Myeloma Patients

text: Multiple myeloma (MM) is a hematological malignancy characterized by an increase in aberrant plasma cells in the bone marrow leading to rising monoclonal protein in serum and urine. With the introduction of novel therapies with manageable side effects, this incurable disease has evolved into a chronic disease with an acceptable quality of life for the majority of patients. Accordingly, management of acute complications is fundamental in reducing the morbidity and mortality in MM. MM emergencies include symptoms and signs related directly to the disease and/or to the treatment; many organs may be involved including, but not limited to, renal, cardiovascular, neurologic, hematologic, and infectious complications. This review will focus on the numerous approaches that are aimed at managing these complications.


title: Biological Functions of IgA

text: Immunoglobulin A (IgA) is the most enigmatic of immunoglobulins. It is by far the most abundant of human Igs, being present in the blood plasma at concentrations approximating 2–3mg/mL, as well as the dominant isotype in most secretions where its output amounts to some 5–8g/day in adults. Furthermore, its evolutionary origins appear to precede the synapsid– diapsid divergence in tetrapod phylogeny (>300 million years ago) because it is present in both mammals and birds and therefore possibly also in reptiles (reviewed in Peppard et al., 2005); an IgA-like molecule has now been identified in a lizard (Deza et al., 2007).


title: Nitric Oxide in TMEV

text: We and others have previously investigated the role of inducible nitric oxide synthase (iNOS) on early acute and late chronic demyelinating disease induced by Theiler’s Murine Encephalomyelitis Virus (TMEV). Infection of susceptible SJL mice with this virus serves as an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). iNOS transcripts and protein were detected in brains and spinal cords of TMEV-infected SJL mice during early acute disease, which resembles polioencephalomyelitis. Similar level of expression of iNOS has been found in resistant B6 mice, which develop only early acute disease. Weak iNOS staining was detected in reactive astrocytes and in leptomeningeal infiltrates in TMEV-infected SJL mice at 42 days post infection (p.i.), corresponding to early phase of chronic demyelinating disease, but not at 66 and 180 days p.i. corresponding to advanced and terminal stages of the disease, respectively. Results from other laboratories demonstrated that, blocking of NO by treatment of TMEV-infected SJL mice with amino guanidine (AG), a specific inhibitor of NO resulted in delay of late chronic demyelinating disease. However this protective effect of NO inhibitor depended on the temporal phase of the disease, type of cells expressing iNOS and the time of administration of AG. The results from our laboratory suggests that NO expressed during early acute disease is beneficial to the host through induction of apoptosis of infiltrating T cells and resolution of encephalitis, but its role in myelin/oligodendrocytes damage during late chronic demyelinating disease is not clear and it may depend on availability of superoxide and formation of peroxynitrite.


title: The fading trail of the sleepy wraith

text: Encephalitis lethargica was an enigma throughout its one and only epidemic. All those who have concerned themselves with this disease have been impressed, above all, by its strangeness — no fiction author would have had the temerity to invent a disorder of such incredible clinical diversity and puzzling behavior — and then the mystery was deepened, and its solution perhaps rendered inaccessible, by its unexpected disappearance. The influenza pandemic of 1918/19 killed many more people, and polio made an especially terrifying impression as a crippling disorder of childhood, but EL retains a special place in the history of brain disease because of its peculiar acute face, the fascinating horror of its intermediate and chronic stages, and the uncertainty of both its origins and its withdrawal.


title: Health Information in the Background: Justifying Public Health Surveillance Without Patient Consent

text: Often we think of collecting, storing, and using health data without patient consent as unethical and illegal. However, there are situations where the collection of health information without consent is not only ethical and legal, it is essential for community and public health. Public health surveillance – the ongoing, systematic collection, analysis, and interpretation of health-related data with the a priori purpose of preventing or controlling disease or injury, or identifying unusual events of public health importance, followed by the dissemination and use of information for public health action – allows the government to meet its ethical obligation to protect the health of the population. By adhering to public health ethics principles, public health surveillance systems, including pervasive information and computing technology (PICT), can be designed and implemented in ways that both honor individuals and protect communities.


Global Supply Chain Networks and Risk Management: A Multi-Agent Framework


title: Role of Zinc and Selenium in Oxidative Stress and Immunosenescence: Implications for Healthy Aging and Longevity

text: Aging is a complex process that includes gradual and spontaneous biochemical and physiological changes which contributes to a decline in performance and increased susceptibility to diseases. Zn and Se are essential trace elements that play a pivotal role in immune functions and antioxidant defense and, consequently, are claimed to play also a role in successful aging trajectories. Consistently with their nature of essential trace elements, a plethora of data obtained “in vitro” and “in vivo” (in humans and animal models) support the relevance of Zn and Se for both the innate and adoptive immune response. Moreover, Zn and Se are strictly involved in the synthesis and regulation of activity of proteins and enzymes, e.g., metallothioneins (MT) and glutathione peroxidase (GPX), that are necessary for our endogenous antioxidant response. This is clearly important to protect our cells from oxidative damage and to slow the decline of our immune system with aging. Age-related changes affecting tissue levels of Zn and Se may indicate that the risk of Zn and Se deficiency increases with aging. However, it is still unclear which of these changes can be the consequence of a “real deficiency” and which can be part of our physiological compensatory response to the accumulating damage occurring in aging. Furthermore, the upregulation of antioxidant proteins (Zn and Se dependent) may be a manifestation of self-induced oxidative stress. By the way, Zn and Se dependent proteins are modulated not only by nutritional status, but also by well-known hallmarks of aging that play antagonistic functions, such as the deregulated nutrient sensing pathways and cellular senescence. Thus, it is not an easy task to conduct Zn or Se supplementation in elderly and it is emerging consistent that these kind of supplementation requires an individualized approach. Anyway, there is consistent support that supplementation with Zn using doses around 10 mg/day is generally safe in elderly and may even improve part of immune performances in those subjects with a baseline deficiency. Regarding Se supplementation, it may induce both beneficial and detrimental effects on cellular immunity depending on the form of Se, supplemental dose, and delivery matrix. The nutritional association of supplements based on “Zn plus Se” is hypothesized to provide additional benefits, but this will likely need a more complex individualized approach. The improvement of our knowledge around screening and detection of Zn and Se deficiency in aging could lead to substantial benefits in terms of efficacy of nutritional supplements aimed at ameliorate performance and health in aging.


title: The Internationalization Challenge: Where to Access Innovation

text: Pharma innovation is becoming increasingly global, partly due to the lure of serving new markets, partly because of the need to access early new technology and talent wherever it emerges. Apart from the established centers of innovation in the United States, Europe and Japan, India, China and Singapore are rising attractors for global life science R&D. China as a pharma market and host of pharma R&D is highlighted as a case study, both from the angle of foreign R&D investors and from the perspective of indigenous Chinese players. Given the significant cost pressures in mature markets, reverse innovation in healthcare has drawn considerable attention by local governments.


title: Pharmaceutical Drug Discovery: Designing the Blockbuster Drug

text: Twenty years ago, drug discovery was a somewhat plodding and scholastic endeavor; those days are gone. The intellectual challenges are greater than ever but the pace has changed. Although there are greater opportunities for therapeutic targets than ever before, the costs and risks are great and the increasingly competitive environment makes the pace of pharmaceutical drug hunting range from exciting to overwhelming. These changes are catalyzed by major changes to drug discovery processes through application of rapid parallel synthesis of large chemical libraries and high-throughput screening. These techniques result in huge volumes of data for use in decision making. Besides the size and complex nature of biological and chemical data sets and the many sources of data “noise”, the needs of business produce many, often conflicting, decision criteria and constraints such as time, cost, and patent caveats. The drive is still to find potent and selective molecules but, in recent years, key aspects of drug discovery are being shifted to earlier in the process. Discovery scientists are now concerned with building molecules that have good stability but also reasonable properties of absorption into the bloodstream, distribution and binding to tissues, metabolism and excretion, low toxicity, and reasonable cost of production. These requirements result in a high-dimensional decision problem with conflicting criteria and limited resources. An overview of the broad range of issues and activities involved in pharmaceutical screening is given along with references for further reading.


title: The Naming of the Faculty

text: Ever since its establishment in 1911, The University of Hong Kong has relied on government funding. The Asian financial crisis caused serious government budget deficits and funding for higher education was sharply reduced. Both the government and the university realized that it was crucial to seek external private support. Within the university, many realized that reliance on the government meant survival but not growth. Philanthropists, in particular Li Ka-shing, became the target of fundraisers. In 2005, he made a very generous gift of HK$1 billion to the university; in turn, the university named the medical faculty after him. This stirred up a storm as critics accused the university of selling off its “ancestral shrine.” This controversy subverted the original intent of the gift, but despite this, the philanthropist’s support of the university continued. Today, the university has forged an East-West Alliance consisting of leading global institutions that had benefited from Li’s generosity, and high-level exchanges are conducted on this platform.


title: Autoimmune Processes in the Central Nervous System

text: In this chapter we discuss the factors that contribute to the unique immunological environment of the central nervous system and the mechanisms that may account for the development of autoimmunity within the CNS, including infectious agents as inducers of autoimmune disease. Consideration is given to a variety of human neurological diseases of autoimmune or presumed autoimmune etiology: autism, neuromyelitis optica, neuromyotonia, schizophrenia, lethargic encephalitis and stiff‐man syndrome. Also, we discuss autoimmunity as a possible mediator of CNS repair and examples of the protective effects of bacterial and helminth infections on CNS disease. Multiple sclerosis and models of multiple sclerosis are discussed with special attention given to the Theiler's virus‐induced demyelination model.


DATA MODEL INTEGRATION: THE GLOBAL EPIDEMIC AND MOBILITY FRAMEWORK


title: One Health and Food Safety

text: Many, if not most, of all important zoonoses relate in some way to animals in the food production chain. Therefore food becomes an important vehicle for many zoonotic pathogens. One of the major issues in food safety over the latest decades has been the lack of cross-sectoral collaboration across the food production chain. Major food safety events have been significantly affected by the lack of collaboration between the animal health, the food control, and the human health sector. One Health formulates clearly both the need for, and the benefit of cross-sectoral collaboration. Here we will focus on the human health risk related to zoonotic microorganisms present both in food animals and food derived from these animals, and typically transmitted to humans through food. Some diseases have global epidemic—or pandemic—potential, resulting in dramatic action from international organizations and national agricultural- and health authorities in most countries, for instance as was the case with avian influenza. Other diseases relate to the industrialized food production chain and have been—in some settings—dealt with efficiently through farm-to-fork preventive action in the animal sector, e.g. Salmonella. Finally, an important group of zoonotic diseases are ‘neglected diseases’ in poor settings, while they have been basically eradicated in affluent economies through vaccination and culling policies in the animal sector, e.g. Brucella. Here we will discuss these three different foodborne disease categories, paying extra attention to the important problem of antimicrobial resistance (AMR). In addition, we present some of the One Health inspired solutions that may help reduce the threat of several of the foodborne diseases discussed.


title: Virology

text: NIAD supports a broad spectrum of both basic and applied research in virology to expand the understanding of the biology, pathogenesis, and the immunology of viral diseases, leading to their prevention, control, and treatment, including research on (i) the viral replication cycle; (ii) the structure and function of the viral components; (iii) host virus interactions, including pathogenesis, immune evasion, and immune enhancement; (iv) viral genetics and evolution; (v) viral interference and defective interfering particles; (vi) virus vector relationships; (vii) epidemiology and natural history; and (viii) preclinical and clinical research to develop vaccines, adjuvants, therapeutics, immunomodulators, and diagnostics (http://www3.niaid.nih.gov/research/topics/viral/introduction.)


docid: ximzvqbm

title: Chargaff’s GC rule

text: Evolutionary selective pressures sometimes act to preserve nucleic acid features at the expense of encoded proteins. That this might occur in the case of nucleic acid secondary structure was noted in Chapter 5. That this might also apply to the species-dependent component of the base composition, (G+C)%, was shown by Sueoka in 1961 [2]. The amino acid composition of the proteins of bacteria is influenced, not only by the demands of the environment on the proteins, but also by the (G+C)% of the genome encoding those proteins.


title: Acute Respiratory Failure in the Oncologic Patient: New Era, New Issues

text: Recent decades have seen an increase in the number of patients living with cancer. This trend has resulted in an increase in intensive care unit (ICU) utilization across this population [1]. Acute respiratory failure is the most frequent medical complication leading to critical illness in oncologic patients [2–4]. Historically, there had been a reluctance to admit cancer patients to the ICU given their poor outcomes, particularly in the setting of hematologic malignancy and invasive mechanical ventilation [5]. ICU treatment limitations or refusal of admission was advocated [6]. Major advances in oncologic care, critical care and more meticulous attention to where the conditions overlap, have resulted in marked improvement in short-term survival in this population [1, 7, 8]. Despite these major advances, acute respiratory failure in this population remains complex with unique challenges surrounding diagnosis and management compared to the general ICU population. This chapter provides a comprehensive overview of acute respiratory failure in the oncologic population and highlights specific considerations for the intensivist. We will focus on the important differences between the immunocompromised oncologic patient and general intensive care population, the spectrum of causes of acute respiratory failure with a specific focus on toxicities related to newer cancer therapies, diagnostic approach, management and an up-to-date overview of prognosis.


title: Recombination in the TYLCV Complex: a Mechanism to Increase Genetic Diversity. Implications for Plant Resistance Development

text: Mutation, reassortment, and recombination are the major sources of genetic variation of plant viruses (García-Arenal et al., 2001; Worobey & Holmes, 1999). During mixed infections, viruses can exchange genetic material through recombination or reassortment of segments (when the parental genomes are fragmented) if present in the same cell context of the host plant. Hybrid progeny viruses might then arise, some of them with novel pathogenic characteristics and well adapted in the population that can cause new emerging diseases. Genetic exchange provides organisms with a tool to combine sequences from different origins which might help them to quickly evolve (Crameri et al., 1998). In many DNA and RNA viruses, genetic exchange is achieved through recombination (Froissart et al., 2005; Martin et al., 2005). As increasing numbers of viral sequences become available, recombinant viruses are recognized to be frequent in nature and clear evidence is found for recombination to play a key role in virus evolution (Awadalla, 2003; Chenault & Melcher, 1994; Moonan et al., 2000; Padidam et al., 1999; Revers et al., 1996; García-Arenal et al., 2001; Moreno et al., 2004). Understanding the role of recombination in generating and eliminating variation in viral sequences is thus essential to understand virus evolution and adaptation to changing environments Knowledge about the existence and frequency of recombination in a virus population might help understanding the extent at which genes are exchanged and new virus variants arise. This information is essential, for example, to predict durability of genetic resistance because new recombinant variants might be formed with increased fitness in host-resistant genotypes. Determination of the extent and rate at which genetic rearrangement through recombination does occur in natural populations is also crucial if we use genome and genetic-mapping information to locate genes responsible of important phenotypes such as genes associated with virulence, transmission, or breakdown of resistance. Therefore, better estimates of the rate of recombination will facilitate the development of more robust strategies for virus control (Awadalla, 2003).


title: Infectieziekten

text: In de vorige eeuw heerste gedurende een korte periode de optimistische opinie dat infectieziekten dankzij vaccinatie en antibiotica overwonnen waren. Al snel werd duidelijk dat dit helemaal niet het geval was. Gedurende de laatste dertig jaar zijn veel nieuwe infectieziekten ontdekt. Humaan immunodeficintievirus, multiresistente Mycobacterium tuberculosis, meticillineresistente Staphylococcus aureus en vancomycineresistente enterokokken hebben zich als nieuwe verwekkers aangediend, terwijl wereldwijd nog altijd velen overlijden aan oude infectieziekten als malaria en darminfecties. De dreiging van wereldwijde epidemien (bijv. influenza) houden de wereld volop bezig.


title: The Way Forward

text: After the March 2004 attacks in Madrid, there can be no doubt that European cities are as likely to be targeted by terrorist activities as their US counterparts. The drafters of the EU constitutional treaty have thus rightly foreseen a solidarity clause providing mutual assistance for EU member states in case of terrorist activities. So far, however, ongoing discussions about improving Europe’s security capabilities have focused primarily on expeditionary tasks while neglecting the provision of homeland security. To overcome this problem, the capabilities of First Responders must receive substantial reinforcement. Here the corporate sector can play a useful role. However, the most substantial reform effort will have to be undertaken by the community of First Responders themselves. By adopting a capabilities-based planning approach, First Responders should jointly identify their capabilities at the international and national levels and set up a capability development mechanism. These actions will help coordinate research, procurement, and training. In doing so, First Responders will be able to assume the much needed role of a credible and capable player to complement NATO’s security and defense policy.


title: The Molecular Biology and Treatment of Systemic Vasculitis in Children

text: Primary systemic vasculitides are rare in childhood but are associated with significant morbidity and mortality. The cause of the majority of vasculitides is unknown, although it is likely that a complex interaction between environmental factors, such as infections and inherited host responses, triggers the disease and determines the vasculitis phenotype. Several genetic polymorphisms in vasculitides have now been described, which may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. This chapter reviews recent studies shedding light on the pathogenesis of vasculitis with emphasis on molecular biology where known, and summarizes current treatment strategies. We discuss new emerging challenges particularly with respect to the long-term cardiovascular morbidity for children with systemic vasculitis and emphasize the importance of future international multicenter collaborative studies to further increase and standardize the scientific base investigating and treating childhood vasculitis.


title: Infectious Disease Informatics and Syndromic Surveillance

text: Infectious disease informatics (IDI) is an emerging field that studies data collection, sharing, modeling, and management issues in the domain of infectious diseases. This chapter discusses various technical components of IDI research from an information technology perspective. Syndromic surveillance is used to illustrate these components of IDI research, as it is a widely-adopted approach to detecting and responding to public health and bioterrorism events. Two case studies involving real-world applications and research prototypes are presented to illustrate the application context and relevant system design and data modeling issues.


title: FIV as a Model for AIDS Vaccine Studies

text: Many experimental strategies have been adopted in experiments to protect cats from FIV infection by vaccination, and some have been successful. The interest in developing a vaccine arose both because FIV is a common cause of morbidity and mortality in pet cats and because the feline virus provides a model for its counterpart in man, human immunodeficiency virus (HIV), for which an effective vaccine is urgently required to halt the current tragic pandemic of acquired immunodeficiency syndrome (AIDS). Shortly after the discovery of FIV and its characterization as a lentivirus, attempts were made to produce a vaccine and success was soon achieved with relatively simple inactivated virus or inactivated virus-infected cell vaccines.82 Further development of this approach led to the introduction in 2002 of the first commercial vaccine against FIV.59 With an estimated prevalence of the infection of up to 25% in populations of pet cats, an effective FIV vaccine could have a significant influence on animal welfare. In addition, this success poses the question of whether a similar strategy might produce an effective vaccine against HIV.


title: Bone Marrow Transplantation

text: Hematopoietic transplantation is increasingly being used as treatment for a variety of severe diseases. Data from International Registries indicate that more than 25,000 transplants are performed every year in Europe, and a similar number in the United States (US) (Copelan 2006; Gratwohl et al. 2007). The objectives of this procedure are: (1) to replace hematopoiesis affected by a severe and irreversible disorder, (2) to rescue the patient from intense marrow toxicity induced by high-dose chemotherapy and/or radiation, and (3) to use a fraction of cells contained in the graft as anti-tumor immunotherapy. Of note, one or more of these objectives may be pursued in a particular situation; for example, in a patient with acute leukemia, transplantation aims to replace the neoplastic hematopoiesis by administering high-dose cytotoxic therapy and taking advantage of the graft-versus-leukemia effect of donor T-lymphocytes from the graft. In contrast, in aplastic anemia the only goal of the procedure is to restore an adequate hematopoiesis.


title: Die Zelle als gengesteuertes System

text: Die genetische Information der Pflanzenzelle ist in den DNA-Molekülen des Zellkerns (nucleäres Genom), der Plastiden (plastidäres Genom) und der Mitochondrien (mitochondriales Genom) niedergelegt. Die Genome der Plastiden und Mitochondrien leiten sich von Genomen prokaryotischer Organismen ab, die während der Evolution als Endosymbionten in die Eukaryotenzelle aufgenommen wurden, Endosymbiontentheorie.Diese Organellengenome, und die zugehörigen Mechanismen der Genexpression, zeichnen sich auch heute noch durch viele prokaryotische Merkmale aus. Andererseits unterscheiden sie sich von den heutigen Prokaryotengenomen z. B. dadurch, dass sie viele Gene an den Zellkern verloren haben, der in der Pflanzenzelle die dominierende Rolle bei der Replication und Transkription der genetischen Information übernommen hat und so viele Funktionen der Organellen steuert. Dieses Kapitel gibt einen Überblick über die Organisation der Genome und die komplexen Mechanismen der Informationsverarbeitung in der Pflanzenzelle, sowie die sich während der Evolution etablierten Abhängigkeitsverhältnisse und Kooperationen zwischen ihren drei genetischen Systemen. Unter Genexpression verstehen wir die Abfolge der molekularen Einzelschritte zwischen einem Gen und seinem reifen Genprodukt, z. B. einem funktionsfähigen Enzym. Dieser Begriff schließt also neben der Transkription (RNA-Synthese) auch die Reifungsprozesse auf der RNA-Ebene, die Translation (Proteinsynthese) und die Mechanismen der Proteinmodifikation und —(in)aktivierung ein. Die auf diesen verschiedenen Ebenen angreifende Regulation der Genexpression liefert die mechanistischen Grundlagen für die Steuerung der Zelldifferenzierung im vielzelligen Organismus und ist daher ein zentrales Thema der molekularen Pflanzenphysiologie.


title: List of Common Abbreviations

text: List of Common Abbreviations


title: Functions of Chikungunya Virus Nonstructural Proteins

text: The nonstructural proteins (nsPs) of chikungunya virus (CHIKV) are expressed as one or two polyprotein precursors, which are translated directly from the viral genomic RNA. Mature nsPs are generated by precise processing of these polyproteins. Both the precursors and mature nsPs are essential for CHIKV replication. Similar to other alphaviruses, CHIKV nsPs not only perform virus RNA replication but are also crucial for other activities essential for virus infection and pathogenesis. Thus far the best-studied CHIKV ns-protein is nsP2, for which protease, NTPase, RNA triphosphatase, and RNA helicase activities have been demonstrated. In addition, nsP2 is crucial for shut-off of host cell transcription and translation and it counteracts cellular antiviral responses. Compared to their homologues from the well-studied Sindbis and Semliki Forest viruses, CHIKV nsP1, nsP3, and nsP4 have been subjected to only few studies. Nevertheless, there are strong indirect pieces of evidence indicating that these CHIKV proteins have the same enzymatic activities as their counterparts in the other alphaviruses. Information concerning the specific interaction of CHIKV nsPs with host components is beginning to emerge. All the nsPs are involved in the functioning of membrane-bound replication complexes also called spherules, but the finer details of the structure and assembly of these complexes are currently poorly understood.


title: A Spatial-Temporal Approach to Differentiate Epidemic Risk Patterns

text: The purpose of disease mapping is to find spatial clustering and identify risk areas and potential epidemic initiators. Rather than relying on plotting either the case number or incidence rate, this chapter proposes three temporal risk indices: the probability of case occurrence (how often did uneven cases occur), the duration of an epidemic (how long did cases persist), and the intensity of a transmission (were the case of chronological significance). By integrating the three indicators using the local indicator of spatial autocorrelation (LISA) statistic, this chapter intends to develop a novel approach for evaluating spatial-temporal relationships with different risk patterns in the 2002 dengue epidemic, the worst outbreak in the past sixty years. With this approach, not only are hypotheses generated through the mapping processes in furthering investigation, but also procedures provided to identify spatial health risk levels with temporal characteristics.


title: Vaccines

text: Since vaccination was documented by Edward Jenner in 1798, it has become the most successful means of preventing infectious diseases, saving millions of lives every year. However, application of vaccines is currently not limited to the prevention of infectious diseases. Vaccines in the pipeline include anti-drug abuse vaccines (nicotine, cocaine) and vaccines against allergies, cancer, and Alzheimer’s disease.


title: Past, Present, and Future of Infectious Diseases

text: Since the existence of human beings in the world, they have been haunted by various infectious diseases. In fact, the history of mankind is also a history about the human fighting against infectious diseases. Infectious diseases are characterized by acute onset, rapid spread, and high mortality rate, which have killed billions of human lives and cause endless disasters to the fortunes and cultures of human beings. For instance, many brilliant cultures, such as the ancient Roman culture, the Maya culture, the Inca culture, and the Marine Polynesian culture, were ruined by plague in a direct or indirect manner. Therefore, people have been struggling to explore the possible causes, epidemic patterns, and pathogenic mechanisms of infectious diseases. In terms of their diagnosis and treatment, from the experience stage to the experiment stage till the present molecular biology stage, more and more knowledge about infectious diseases have been gained and keep on increasing.


title: Framing Infectious Diseases: Effective Policy Implementation and United States Public Opinion

text: This chapter combines quantitative and qualitative research methods—content analysis of newspaper reports and analysis of health opinion polls to assess impact of media frames in shaping public opinion. Focusing on framing of transnational infectious diseases (HIV/AIDS, SARS, and avian flu) as medical dangers, economic risks, security threats, and human rights concerns, the chapter draws attention to the role of media frames in enlisting active support and engaging public opinion for effective policy implementation to control spread of these infectious diseases. The findings also address the debate on the role and importance of domestic public opinion as a factor in domestic and foreign policy decisions of governments in an increasingly globalized world.


title: Resilience in Risk Analysis and Risk Assessment

text: Resilience is the ability of a system to react to and recover from disturbances with minimal effects on dynamic stability. Resilience is needed as systems and organizations become more complex and interrelated and the consequences of accidents and incidents increase. This paper analyzes the notion of resilience based on a literature survey and an exploration of incidents. In particular, resilience involves the ability of systems to undergo graceful and controlled degradation, the ability to rebound from degradation, the presence of redundancy, the ability to manage margins close to the performance boundaries, the establishment and exploration of common mental models, the presence of flexibility in systems and organizations, and the reduction of complexity and coupling. The paper describes how resilience can be included in system development and operations by considering organizations, technology and human factors. Also, it shows how past strengths and weaknesses can be considered in risk analysis to enhance safety, security and resilience.


Macrosocial Determinants of Population Health in the Context of Globalization


Replication of Plus-Sense Viral RNA


title: Bioterrorism Alert for Health Care Workers

text: When the agent used in a biological attack is known, response to such an attack is considerably simplified. The first eight chapters of this text deal with agent-specific concerns and strategies for dealing with infections due to the intentional release of these agents. A larger problem arises when the identity of an agent is not known. In fact, in some cases, an attack may be threatened or suspected, but it may remain unclear as to whether such an attack has actually occurred. Moreover, it may be unclear whether casualties are due to a biological agent, a chemical agent, or even a naturally occurring infectious disease process or toxic exposure. Recent experience with West Nile Virus (Fine and Layton, 2001), Severe Acute Respiratory Syndrome (SARS) (Lampton, 2003), and monkeypox highlight this dilemma. In each of these cases, the possibility of bioterrorism was raised, and rightly so, although each outbreak ultimately proved to have a natural origin. This chapter provides a framework for dealing with outbreaks of unknown origin and etiology. Furthermore, it addresses several related concerns and topics not covered elsewhere in this text.


title: Septic Shock

text: For more than 20 years, sepsis has been defined as symptoms associated with the response to microorganism infection, which was more specifically called systemic inflammatory response syndrome (SIRS). With the evidence of organ failure, it was called severe sepsis, and this could lead to hypotension (septic shock). However, with the deep understanding of the pathophysiology of sepsis, sepsis has been known as both inflammatory and anti-inflammatory. Additionally, the classic use of SIRS could lead to overestimation of sepsis. For example, usual common cold could be identified as sepsis in classic definition. With this background, new sepsis definition, Sepsis 3, was introduced and sepsis was defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The management of sepsis has been changed dramatically, with the development of Surviving Sepsis Campaign, which substantially increased the survival of sepsis. However, this is not with the help of a new drug, but the implementation of a treatment system. Unfortunately, no specific drug for sepsis has survived in clinical use even though many candidate drugs have been successfully investigated in preclinical setting, and this leads to the new approach to the sepsis.


title: Allgemeine Notfälle

text: In diesem Kapitel werden Fragen zu allgemeinen Notfallsituationen gestellt, beispielsweise zu zerebralen, kardiozirkulatorischen und respiratorischen sowie gastrointestinalen und abdominalen Notfällen, Notfällen bei Kindern sowie bei Schwangeren und Neugeborenen. Auch HNO-, ophtalmologische, urologische und traumatologische Notfälle werden behandelt.


title: Survival of Viruses in the Marine Environment

text: It has been well established that human pathogenic viruses may be transmitted through the marine environment due to the release of sewage by polluted rivers, outfalls, or release from vessels. These wastes contain human enteric viruses, which if ingested, or in some cases inhaled, can cause a wide variety of illnesses. Their ability to be transmitted by this route is because of their capability to remain infectious long enough in the marine environment to come in contact with a susceptible host. Transmission routes may be fairly direct, such as ingested of contaminated seawater by a swimmer, or more complex by prolonged survival in sediments which are later resuspended and accumulated in shellfish during feeding. The virus is then transmitted during consumption of the shellfish. To understand the potential for human enteric virus transmission through the marine environment numerous studies have been conducted on factors which influence their persistence in this environment (Table 6.1). This reviewfocuses on factors that could play a role in the survival of human pathogenic viruses in the marine environment.


title: Intensive Care Medicine: Where We Are and Where We Want To Go?

text: Intensive care medicine can be defined as the science and art of detecting and managing patients with impending or established critical illness, in order to prevent further deterioration and revert the disease process or its consequences, so as to achieve the best possible outcomes.


title: Component-Based Modelling of RNA Structure Folding

text: RNA structure is fundamentally important for many biological processes. In the past decades, diverse structure prediction algorithms and tools were developed but due to missing descriptions in clearly defined modelling formalisms it’s difficult or even impossible to integrate them into larger system models. We present an RNA secondary structure folding model described in ml-Devs, a variant of the Devs formalism, which enables the hierarchical combination with other model components like RNA binding proteins. An example of transcriptional attenuation will be given where model components of RNA polymerase, the folding RNA molecule, and the translating ribosome play together in a composed dynamic model.


title: Screening and Surveillance for Promoting Population Health

text: 1. Distinguish between screening and surveillance activities. 2. Interpret the accuracy of a screening test. 3. Identify limitations associated with screening for a health problem. 4. Plan a surveillance system based upon known risk factors for a health problem. 5. Identify limitations of a surveillance system.


title: Prevention of Infections in Patients with Hematological Malignancies

text: Infection is a major complication of patients with hematological malignancies. Prophylaxis is a key element in the management of these patients, and is composed by two main components: infection control measures and antimicrobial chemoprophylaxis. Infection control measures are safe, but not always effective. Antimicrobial prophylaxis is usually effective but may increase resistance rates, toxicity, and cost. Therefore, a careful evaluation of the actual risk for infection, the pathogens that predominate in a particular setting, and the periods at risk are important in order to define the most appropriate strategy. In this chapter we review the most important parameters to assess the risk on an individual basis, and the evidences and recommendations supporting infection control measures and antimicrobial prophylaxis against bacteria, fungi, viruses, and parasites.


title: Primary Immunodeficiencies

text: Primary immunodeficiencies (PIDs), once considered to be very rare, are now increasingly recognized because of growing knowledge in the immunological field and the availability of more sophisticated diagnostic techniques and therapeutic modalities [161]. However in a database of >120,000 inpatients of a general hospital for conditions suggestive of ID 59 patients were tested, and an undiagnosed PID was found in 17 (29%) of the subjects tested [107]. The publication of the first case of agammaglobulinemia by Bruton in 1952 [60] demonstrated that the PID diagnosis is first done in the laboratory. However, PIDs require specialized immunological centers for diagnosis and management [33]. A large body of epidemiological evidence supports the hypothesis of the existence of a close etiopathogenetic relation between PID and atopy [73]. In particular, an elevated frequency of asthma, food allergy (FA), atopic dermatitis and enteric pathologies can be found in various PIDs. In addition we will discuss another subject that is certainly of interest: the pseudo-immunodepressed child with recurrent respiratory infections (RRIs), an event that often requires medical intervention and that very often leads to the suspicion that it involves antibody deficiencies [149].


title: Nasal Cavity and Paranasal Sinuses

text: The nasal cavity and paranasal sinuses occupy the top of the upper respiratory tract and form pneumatic spaces connected with the atmosphere. They are located immediately beneath the base of the cranium, where crucial vital structures are harbored. From this region, very much exposed to airborne agents, arise some of the more complex and rare benign and malignant lesions seen in humans, whose difficulties in interpretation make this remarkable territory one of the most challenging in the practice of surgical pathology. Contents of this chapter cover inflammations and infections, polyps and pseudotumors, fungal and midfacial destructive granulomatous lesions, as well as benign, borderline, and malignant neoplasms. Among the neoplasms, emphasis is made on those entities characteristic or even unique for the sinonasal region, such as Schneiderian papillomas, glomangiopericytoma, intestinal- and non-intestinal-type adenocarcinomas, olfactory neuroblastoma, nasal-type NK-/T-cell lymphoma, and teratocarcinosarcoma. Moreover, recently recognized entities involving this territory, i.e., HPV-related non-keratinizing carcinoma, NUT carcinoma, and SMARCB1-deficient basaloid carcinoma, are also discussed in the light of their specific molecular findings. Furthermore, the text is accompanied by numerous classical and recent references, several tables, and 100 illustrations.


title: Risk Assessment for Foodborne Viruses

text: Risk is an inherent component of human existence, as is our creation of ways to avoid or minimize such risks. The formal process of assessing the likelihood and magnitude of risk, using that information to manage risk, and then communicating the process to others, forms the basis for risk analysis. This chapter provides an overview of the steps of risk analysis with a focus on risk assessment for foodborne viruses, particularly quantitative efforts that model and estimate the risks these viruses pose to human health. Most risk assessments in food and environmental virology performed in the last decade have focused on water, fresh produce, molluscan shellfish, and prepared foods. Recent examples of enteric virus risk modeling efforts are discussed in detail, as are several of the difficulties and intricacies of performing risk assessments for foodborne viruses compared to bacteria and other agents. This is a relatively new area of study, but one that will continue to grow as national and international agencies continue to adopt and require the methodology for food safety and the protection of human health.


Co-Infection with HIV and Tuberculosis


title: Free Radicals and Medicine

text: EPR has been employed in attempts to understand the basis of specific pathophysiologies in which free radicals have a postulated role. Examples described include pulmonary free radical damage, free radicals and sickle cell disease, free radicals in amyotrophic lateral sclerosis, melanin and free radicals and the potential role of oxidative stress in the induction of cancer. The final section of the chapter describes the use of NMR as the spectroscopic measure of spin-trapped radicals, after they have reacted further to form diamagnetic species.


title: Il recettore AT2: gli effetti

text: La dimostrazione che anche i recettori AT2 producono effetti importanti, ed in linea di massima opposti a quelli prodotti dai recettori AT1, è arrivata solo in questi ultimi anni (de Gasparo e coll. 2000; Stoll e Unger 2001), quando con metodiche di tipo diverso è stato accertato che questi effetti sono molteplici, perché interessano i livelli pressori e l’attività miocardica, i processi proliferativi e l’apoptosi, la funzione renale, alcune funzioni del SNC ed alcuni parametri metabolici, in pratica tutti i fattori dai quali dipende la omeostasi (Unger 1999; Carey e coll. 2005a eb) (Tabella 4). [Figure: see text]


Krim-Fieber


title: Bioinformatics and Microarray-Based Technologies to Viral Genome Sequence Analysis

text: Identification of microbial pathogen is an important event which lead to diagnosis, treatment, and control of infections produce by them. The high-throughput technology like microarray and new-generation sequencing machine are able to generate huge amount of nucleotide sequences of viral and bacterial genome of both known and unknown pathogens. Few years ago it was the DNA microarrays which had great potential to screen all the known pathogens and yet to be identified pathogen simultaneously. But after the development of a new generation sequencing, technologies and advance computational approach researchers are looking forward for a complete understanding of microbes and host interactions. The powerful sequencing platform is rapidly transforming the landscape of microbial identification and characterization. As bioinformatics analysis tools and databases are easily available to researchers, the enormous amount of data generated can be meaningfully handled for better understanding of the microbial world. Here in this chapter, we present commentary on how the computational method incorporated with sequencing technique made easy for microbial detection and characterization.


title: Abdominal Pain

text: Wide range of pathologies may present with abdominal pain. Key to reach proper diagnosis is adequate history and physical examination along with laboratory tests and imaging. Disposition of patients with abdominal pain is as difficult as its diagnosis. Low threshold should be kept for high-risk patients. Life-threatening diseases should not be missed in emergency.


title: Epidemiological Interaction at the Wildlife/Livestock/Human Interface: Can We Anticipate Emerging Infectious Diseases in Their Hotspots? A Framework for Understanding Emerging Diseases Processes in Their Hot Spots

text: Emerging infectious diseases’ hotspots have been identified as multi-host and multi-pathogen systems often characterized in tropical ecosystems by an extensive wildlife/domestic/human interface. The pathogen communities shared by the wild and domestic populations at this interface reflect the historical epidemiological interactions between them. In a research framework using recent community ecology, evolutionary biology and molecular biology advances, this information can be used to identify potential pathways for future pathogen spill-over initiating the emergence process. In other words, an understanding of the mechanisms of pathogen transmission in a specific ecosystem can provide an interaction network between host populations defined by nodes and edges and characterized by the frequency, intensity and direction of the interactions with a direct input for targeted disease surveillance.


title: The Socio-economic Context that Ecological Aesthetics Produces

text: The necessity of the economy and society produced by ecological aesthetics must explain whether the form of human civilization should achieve a new transition from industrial civilization to ecological civilization.


title: A Health Policy Simulation Model of Ebola Haemorrhagic Fever and Zika Fever

text: This study proposes a simulation model of a new type of infectious disease based on Ebola haemorrhagic fever and Zika fever. SIR (Susceptible, Infected, Recovered) model has been widely used to analyse infectious diseases such as influenza, smallpox, bioterrorism, to name a few. On the other hand, Agent-based model begins to spread in recent years. The model enables to represent behaviour of each person in the computer. It also reveals the spread of an infection by simulation of the contact process among people in the model. The study designs a model based on Epstein’s model in which several health policies are decided such as vaccine stocks, antiviral medicine stocks, the number of medical staff to infection control measures and so on. Furthermore, infectious simulation of Ebola haemorrhagic fever and Zika fever, which have not yet any effective vaccine, is also implemented in the model. As results of experiments using the model, it has been found that preventive vaccine, antiviral medicine stocks and the number of medical staff are crucial factors to prevent the spread. In addition, a modern city is vulnerable to Zika fever due to commuting by train.


title: Immunological Defence Mechanisms Against Biological Agents

text: A short discussion about attack strategies by microorganisms and immunological defence mechanisms by human body: facts and concepts for preventing disease and biological warfare.


title: Scenario Discovery Using Nonnegative Tensor Factorization

text: In the relatively new field of visual analytics there is a great need for automated approaches to both verify and discover the intentions and schemes of primary actors through time. Data mining and knowledge discovery play critical roles in facilitating the ability to extract meaningful information from large and complex textual-based (digital) collections. In this study, we develop a mathematical strategy based on nonnegative tensor factorization (NTF) to extract and sequence important activities and specific events from sources such as news articles. The ability to automatically reconstruct a plot or confirm involvement in a questionable activity is greatly facilitated by our approach. As a variant of the PARAFAC multidimensional data model, we apply our NTF algorithm to the terrorism-based scenarios of the VAST 2007 Contest data set to demonstrate how term-by-entity associations can be used for scenario/plot discovery and evaluation.


docid: ibeqoltn

title: Intensive Care Management of Severe Acute Liver Failure

text: Severe acute liver failure is defined as the development of overt liver failure with encephalopathy over eight weeks or less in previously healthy individuals. In hyperacute liver failure, deterioration occurs in less than 14 days. Whilst it is a relatively uncommon reason for admission to the intensive care unit (ICU), acute liver failure is important because it often occurs in previously well young adults and carries a high mortality. Management of these patients presents considerable challenges within the ICU due to the extreme nature of the associated pathophysiological processes, which affect multiple systems. Integrated management strategies have been poorly studied and treatment is often center-specific [1]. Clinical manifestations include a reduced conscious state, jaundice with abnormal liver function tests (especially elevations in amino acid transferase levels more than 25 times the upper limit of normal) and coagulopathy. Further deterioration can involve marked cerebral edema, hypoglycemia and severe shock with lactic acidosis and multiple organ failure. The use of clinical management guidelines may assist in the treatment of these patients by providing an evidence-based framework for care by staff at the bedside, which ensures that all important priorities are adequately addressed. It is possible that a coordinated combination of specific and general therapies may reduce mortality and the need for liver transplantation. Consideration for transfer to a unit with expertise in liver transplantation may be appropriate in order for this option to be available as a life-saving treatment should supportive care fail to arrest deterioration.


title: 21 Infecties, ziekte en zwangerschap

text: Chronische ziekten en infecties vormen een belangrijke oorzaak van maternale en foetale morbiditeit en mortaliteit. Een goede voorbereiding op de interactie tussen de zwangerschap en het onderliggend lijden kan dit mogelijk verbeteren. Preconceptionele advisering, multidisciplinaire behandeling en het treffen van goede voorzorgsmaatregelen in het geval van complicaties maken hier een belangrijk onderdeel van uit. Kennis van de fysiologische veranderingen die optreden tijdens de zwangerschap, is hiervoor onontbeerlijk. Infecties vormen tijdens de zwangerschap een reëel gevaar voor de gezondheid van moeder en kind. Preventie en zo mogelijk tijdige behandeling is obligaat.


title: Is de kans groot dat een verkouden huisarts zijn patiënten aansteekt?

text: Volwassenen in de leeftijdsgroep vanaf 30 jaar krijgen per jaar per persoon gemiddeld 1-2 acute luchtweginfecties (1). De aard van het beroep van huisarts kan betekenen dat dit aantal voor huisartsen hoger ligt maar daarover is weinig informatie bekend. Ter vergelijking: kinderen van 0-2 jaar krijgen gemiddeld tussen de 5 en 6 acute luchtweginfecties per jaar (1).


title: Infection and Inflammation: Catalysts of Pulmonary Morbidity in Bronchopulmonary Dysplasia

text: Bronchopulmonary dysplasia (BPD) is the most frequent pulmonary morbidity among survivors of prematurity. While the precise cause remains unknown, both antenatal factors, and specifically chorioamnionitis, as well as bacterial sepsis, cytomegalovirus infection, and respiratory viral infections have been associated with the pathogenesis of BPD. This chapter will focus on the impact that inflammation and infection have on the development of BPD in preterm infants and its long-term pulmonary morbidities. Knowledge of the respiratory tract microbiome and virome and their role in the development of BPD constitutes a major knowledge gap in our continuing efforts to decrease the incidence of BPD and its consequences.


title: Bioactive Marine Alkaloids

text: The chapter deals with bioactive marine alkaloids. The chemistry and biological activities of pyridoacridines, pyrroloacridines, indoles, β-carbolines, pyrroles, isoquinolines, and tyrosine derived alkaloids have been discussed and reviewed.


title: The OIE Strategy to Address Threats at the Interface Between Humans, Animals and Ecosystems

text: In our globalised, fast-changing world (deforestation, fast-growing animal protein demand, etc.), animal diseases that have an impact on public health, livelihoods, food security as well as the international trade of products of animal origin are constantly emerging or re-emerging. The complexity of disease emergencies calls for the identification of often collaborative effective strategies, based on both science and proven practical experience, to reduce future threats. The H(5)N(1) avian influenza crisis has shown how crucial it is to address persistent global threats at the interface between humans, animals and ecosystems which requires (i) to strengthen animal and human health institutions and (ii) build strong partnerships among players who may have different perspectives on some issues and different levels of resources. To address the gaps in the animal health sector, OIE seeks to build member countries’ capacities in policy design and good governance in animal health systems and Veterinary Services. At policy level, the OIE helps its members to enhance their credibility, both at the national and international level, by providing them with efficient tools, such as the strategic planning tools of the Performance of Veterinary Services (PVS) Pathway, with the objective to attract more commitment and more resources from their decision makers and partners. At good governance level, it provides science-based guidance that supports members in detecting, preventing and managing serious animal disease outbreaks through improved surveillance systems, strengthened laboratory networks and improved legislation. OIE promotes strong partnerships, notably with FAO and WHO, especially with regard to two topics that are getting currently a great attention and that require a strong multi-sectoral collaboration at all levels because of their social, economical and ecological determinants: rabies in humans that still kills more than 50,000 persons every year, mainly in Asia and mostly youngsters, and that is believed to be totally preventable through effective dog vaccination, and antimicrobial resistance that can hinder the effective treatment and recovery of illnesses in both humans and animals. At regional level and in full collaboration with ASEAN and other partners, the OIE Sub-Regional Representation (OIESRR) for Southeast Asia plays a significant role in regional coordination of animal health and emerging infectious disease management in a region that is often considered as a ‘hotspot’ for emergence. Along the strategic objectives of the OIE Fifth Strategic Plan, the implementation of its activities to achieve the OIE Strategic Objectives is supported by various programmes and projects funded by donors. Its long-standing flagship regional programme, the Southeast Asia and China Foot-and-Mouth Disease (SEACFMD) Campaign which aims at controlling FMD by 2020 through vaccination promotes socio-economical and participatory approaches as well as assessment of the role of wildlife.


title: Flourishing

text: Being part of, or witnessing, a terrible disaster is clearly very distressing. How do we minimize this kind of distress and continue to flourish in the future as we face extreme climate events such as wildfires and flooding? How do we identify and learn from past events lying hidden, unrecognized and unforeseen as failure incubated? What are the global ‘grand challenges’—both natural and man-made? What are the UN Sustainable Development Goals? To achieve them do we need to reverse the fragmentation of the professions into ‘silos’? What is ‘joined-up’ thinking in ‘joined-up’ organisations and nation states and how important is it? Despite all the advances in science, we know less actually than we think we know. Contingency planning that expects surprises must be the new norm. Learn anew how to learn together is the new wisdom. Use the golden rule ‘do not do to others that you would not have them do to you’, whatever you are told to believe, is our tenet. Behaviour is more important than belief—imperfect doing is better than uncertain knowing. But to do all of this collectively requires leadership that we can trust—perhaps the biggest challenge of all?


title: A One Health Approach to Wildlife and Food Safety

text: Global health problems including the assurance of safe and secure food are becoming more numerous and complex and require sensitive and transdisciplinary problem solving efforts. One Health provides the framework to approach food safety risks from the whole ecosystem of the food system by using a Web of Causation approach instead of an ‘us vs. them’ approach. This whole ecosystem, One Health approach focuses on prevention through the integration of wildlife, environmental, human, and domestic health sectors improving our ability to prevent rather than react to disease events. A true One Health viewpoint understands that all life is connected to its habitat, and the health of the whole sits squarely on a robust and sustainable environment. Safe food and water, thus ecological health, can be ensured using an evidence-based, transdisciplinary, collaborative based approach to the solution of food production and public health.


title: Vorbereitung des Einsatzes

text: Für den Einsatz eines Bauleiters ist es besonders wichtig, sich auf seine Rolle vorzubereiten, die dazu erforderlichen Vollmachten abzufordern und alle Möglichkeiten der persönlichen Einsatzvorbereitung zu kennen und landesspezifisch zu nutzen. Im Vergleich zum Inlandeinsatz ergeben sich dabei bedeutend höhere Anforderungen für die späteren Aufgaben.


title: Regulatory Aspects in the Development of Gene Therapies

text: Preclinical therapeutics development research is directed toward fulfilling two overlapping sets of goals. A set of scientific goals includes defining the best molecule or biologic construct for the task at hand, and proving the case for its development. The second set of goals addresses regulatory requirements necessary to introduce the agent into human subjects. In the case of “small molecule” drugs, in most cases the identity of the molecule and appropriate safety studies are straightforward. In contrast, the development of biologic agents, including gene therapies discussed here, presents distinct challenges. The nature of the “drug” may be an organism subject to mutation or selection of variants through recombination. Its properties may vary depending on the scale and method of its preparation, purification, and storage. How to test adequately for its safety prior to first introduction in humans may not be straightforward owing to intrinsic differences in response to the agent expected in humans as compared to animals.


title: Obstetric Medicine

text: JOGC 2008 30:3 S1 PREECLAMPSIA—new onset or worsening hypertension, ± proteinuria (≥300 mg/day or ≥30 mg/mmol spot urine protein to creatinine ratio), ± adverse clinical signs or symptoms or abnormal labs. A disease >20 weeks gestation ECLAMPSIA—preeclampsia with generalized tonic clonic seizures


title: Interactive Real-time Image Analysis System for Distant Operation

text: This paper reports on the development and implementation of an integrated and interactive system for cell analysis featuring remote operation and real-time analysis for generating analytical data from microscopic images. The system consists of a number of image processing modules implemented in a virtual instrumentation environment, combined with novel techniques developed for thinning and local edge-gap filling in the cell image segmentation process. These approaches, integrated with advances in networking, have been initially applied to viral feature analysis in SARS-CoV microscopy. Real-time operation through the user-interface of the proposed system generates quantitative results for remote clients. The rapidity and viability of operation permit the investigation of mutant viral agents on the basis of their morphological cell features.


title: Personalized Management of Pulmonary Disorders

text: There are a large number of pulmonary disorders some of which present challenges in management. Role of genetic ancestry in lung function is under investigation. There is still limited information on pharmacogenomics and pharmacogenetics of pulmonary therapeutics. Personalized approaches to some pulmonary diseases will be described briefly as examples in this chapter.


docid: wqkjzipn

title: Epidemiologie

text: Früher wurde der Begriff Epidemiologie für die Lehre von den großen, menschheitsbedrohenden Seuchen benutzt. Heute versteht man darunter die Wissenschaft von allen übertragbaren und nichtübertragbaren Krankheiten in einer Population, unabhängig davon, ob sie zeitlich oder räumlich gehäuft auftreten. Im Bereich der Mikrobiologie befasst sich die Epidemiologie mit Erkrankungen, die durch übertragbare Agenzien wie Bakterien, Viren oder auch Prionen verursacht werden, und zwar insbesondere mit deren Verbreitung und den Infektionsfolgen. Epidemiologische Untersuchungen besitzen somit eine große Bedeutung für die Gesundheit der Weltbevölkerung und sind die Grundlage für allgemein- und seuchenhygienische Maßnahmen wie Quarantäne oder Impfungen zur Verhinderung oder Eindämmung von Pandemien und Epidemien. Sie ermöglichen außerdem die Entwicklung von Richtlinien und Vorschriften für Impfungen und andere Maßnahmen zur Verhütung von Infektionen.


title: Infections in Allogeneic Stem Cell Transplantation

text: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a widely used modality of therapy for a variety of malignant and nonmalignant diseases. Despite advances in pharmacotherapy and transplantation techniques, infection remains one of the most severe and frequently encountered complications of allo-HSCT. This chapter will address the risk factors for development of infection following allo-HSCT, including those related to the host, the conditioning regimen, and the graft, as well as the timing of opportunistic infections after allo-HSCT. The most common bacterial, viral, fungal, and parasitic infections, as well as issues surrounding their diagnostics and treatment, will be discussed. Finally, this chapter will address vaccination and other preventative strategies to be utilized when caring for patients undergoing allo-HSCT.


title: Autoimmune Disease and the Human Metagenome

text: The prevailing theory of autoimmune disease, that the body creates autoantibodies that attack “self,” was developed during an era when culture-based methods vastly underestimated the number of microbes capable of persisting in and on Homo sapiens. Thanks to the advent of culture-independent tools, the human body is now known to harbor billions of microbes whose collective genomes work in concert with the human genome. Thus, the human genome can no longer be studied in isolation. Some of these microbes persist by slowing the activity of the vitamin D receptor nuclear receptor, affecting the expression of endogenous antimicrobials and other key components of the innate immune system. It seems that bacteria that cause autoimmune disease accumulate over a lifetime, with individuals picking up pathogens with greater ease over time, as the immune response becomes increasingly compromised. Any one autoimmune disease is likely due to many different microbes within the metagenomic microbiota. This helps explain the high levels of comorbidity observed among patients with autoimmune conditions. What are commonly believed to be autoantibodies may instead be created in response to this metagenomic microbiota when the adaptive immune system is forced to deal with disintegration of infected cells. Similarly, haplotypes associated with autoimmune conditions vary widely among individuals and populations. They are more suggestive of a regional infectious model rather than a model in which an illness is caused by inherited variation of HLA haplotypes


title: NIV in the Treatment of Acute Respiratory Failure: Controversial Indications

text: A case of pneumonia that requires ventilation, whether invasively or non invasively, is always a serious event associated with a high mortality rate, particularly in the elderly, even though it is often considered by the media as an infection that is “easy” to resolve. Why is this a controversial indication for NIV? Because there are observational studies that are absolutely against the use of NIV and a couple of randomized controlled trial in favor, in theory, but not necessarily in all cases of pneumonia or in all patients.


title: Wildlife Disease Surveillance and Monitoring

text: Emerging diseases of human or veterinary importance are a major challenge to human society. As previously discussed, infectious diseases of wild mammal populations can have significant economic impact, may threaten human and livestock health (Artois et al. 2001), and can affect the welfare and conservation of game (Gortazar et al. 2006) and species of high conservation value (Cleaveland et al. 2002). Wild mammals are also implicated as sources of emerging diseases (Daszak et al. 2000a; Cleaveland 2003; Cunningham 2005). Comprehensive epidemiological investigations and disease surveillance of wild mammal populations will enhance our capaCity to detect and control infectious diseases that may emerge in the future in human and domestic animal populations. Given that the majority of diseases that have emerged in the last couple of decades had a wildlife origin (see Chapter 1), surveillance for wildlife diseases may be seen as an essential tool for the protection of human health. For these reasons, the development of effective programmes for the surveillance of disease in wildlife populations is becoming increasingly important. Epidemiological investigations in wildlife are similar in many respects in terms of their objectives, concepts and methodology to those undertaken for domestic animal health surveillance and monitoring. However, there are also substantial differences, owing to the zoological, behavioural and ecological characteristics of wildlife populations. Consequently, definitions, methods and procedures must often be adapted to suit the unique conditions of wildlife disease surveillance.


Self Assessment Questions


title: General Measures of Infection Control

text: Health-care-associated infections are a common cause of increased morbidity, mortality, and cost of care in ICUs. Infection control and judicious antibiotic use are the mainstay of management of these patients. A systematic and multidisciplinary approach to infection control practices goes a long way in minimizing this problem.


title: Other Transgenic Animal Models Used in Cardiovascular Studies

text: Previous chapters have described a large number of transgenic animal models used to study specific cardiovascular syndromes. This chapter will fill in some gaps. Many of these transgenic animals were developed to study normal and/or abnormal physiological responses in other organ systems, or to study basic biochemical and molecular reactions or pathways. These models were then discovered to also have effects on the cardiovascular system, some of them unanticipated. A word of caution, particularly when highly inbred mouse strains are used to develop transgenic models - not all strains of a particular species are created equal. When cardiovascular parameters of age- and sex-matched A/J and C57BL/6J inbred mice were compared the C57BL/6J mice demonstrated eccentric physiologic ventricular hypertrophy, increased ventricular function, lower heart rates, and increased exercise endurance.(1)


title: The Making of a Modern Endemic: An Introduction

text: “Why Mass Shootings May Be Contagious, New Study Examines”; “Is there an antidote to Emotional Contagion”; “Gaining weight is socially contagious—so is losing it.” In 2015, these headlines appeared alongside those pertaining to Ebola virus disease (EVD), West Nile virus, and the recently infamous “Giant Frozen Virus Still Infectious After 3000 Years.”