title: Translational Recoding and RNA Modifications

text: During protein synthesis, codons in mRNA are translated sequentially in frame on the ribosome following strict decoding rules. This process is usually very accurate. However, in some cases, recoding events occur at selected codons, leading to a high frequency of frameshifting or stop codon readthrough. The factors influencing these noncanonical decoding events are very diverse; among them are the codon usage and context, the presence of a stable mRNA secondary structure downstream of the decoding sites and the type and relative abundance of normally modified tRNA. Here, we discuss the role of certain modified nucleotides of tRNAs in a few cases of frameshifting and readthrough that occur in Bacteria and Eukarya. While in some cases the effect of a given modified nucleotide in a tRNA is to increase accuracy of the recoding process, in a few other cases the reverse has been observed. This review illustrates the power of using well characterized recoding systems, coupled with specific defects of RNA modification enzymes to assay for translational fidelity under in vivo conditions.


title: The Changing Landscape for New Drug Development: Medical Countermeasures (MCMs) as a Case Study

text: This chapter is comprised of materials adapted from previous publications authored by the Center for the Study of Drug Development at Tufts University School of Medicine (Tufts CSDD) over a ten-year period from 2010 through 2019. In addition, there are occasional infusions of updated commentary to “connect the dots” of how we got to where we are today. These publications may be requested from Tufts CSDD (if originally published in-house) or through the usual channels for requesting articles published in the public domain (permission to reprint the articles having been granted, where required). The text of the chapter is structured basically in a chronological fashion beginning with Tufts CSDD analysis of the early era of MCM evolution as a sub-sector from various extant therapeutic areas. It then chronicles the changes to the R&D paradigm in response to the challenges that emerged for both MCMs and biopharma in general. Finally, it ends with an exploration of the devolution of the MCM sub-sector back into its roots in the infectious disease area as an increase in actual outbreaks as well as other signals of global vulnerability to pandemic threats have minimized the MCM emphasis on biodefense against a wide range of CBRN agents in favor of public health tactics to address humankind’s maladaptation to a world in which it is constantly assailed by its microbial competitors and symbionts, or to novel public health crises of its own making.


title: Pathologie

text: Im Rahmen der Pathologie („Lehre der Leiden“) werden Krankheiten aller Fachgebiete und deren grundlegende Prinzipien diagnostiziert und erforscht. Die vitale Diagnostik (am Lebenden) steht dabei immer mehr im Vordergrund.


title: Neuroimaging

text: Imaging of infection in the CNS has been handled using cross-sectional imaging for more than two decades now resulting in a large array of descriptive diagnostic criteria, capable, in most circumstances of narrowing the differential diagnosis, detecting life-threatening complications and establishing baseline for assessment of treatment response. Limitations however exist, and in many circumstances, both cross-sectional imaging and nonspecific molecular imaging, such as (18)F-FDG, fail to establish a diagnosis. The availability of pathogen-specific imaging agents/ligands would have a great effect on the management of patients with CNS infection. Besides early diagnosis, avoidance of diagnostic brain biopsies can have significant effect on the mortality and morbidity of patients.


title: Pandemic

text: Pandemics such as the Black Death have altered the course of history. The ravages of the Spanish Flu pandemic were so terrible that at least one culture decided the most humane way of dealing with the aftermath was simply to ignore it—to pretend the disease had not happened. Could a new pandemic possibly be worse than the Black Death or the Spanish Flu? Could it be as bad as the Scarlet Plague of Jack London’s story?


title: Acute Respiratory Distress Syndrome in Cancer Patients

text: Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU.


title: Arena-Viren

text: Die Gruppe der Arena-Viren (arenosus = körnig) umfasst das LCM-Virus (Meningitis des Menschen), das Virus des Lassa-Fiebers, eines nur in den Tropen vorkommenden schweren hämorrhagischen Fiebers sowie das Virus einer Reihe von südamerikanischen hämorrhagischen Fieber (z. B. Bolivianisches (Machupo-Virus) und Argentinisches (Jun-in-Virus) Hämorrhagisches Fieber).


title: Blut und Blutprodukte

text: die Blutgruppe richtet sich nach der Antigeneigenschaft der Erythrozyten; die Blutgruppenantigene A und B des AB0-Systems befinden sich an der Erythrozytenoberfläche. Das Antigen 0 gibt es nicht, man spricht allenfalls vom Merkmal H; die Blutgruppe A lässt sich in A(1) und A(2) unterteilen. Der Hauptunterschied zwischen den Untergruppen besteht darin, dass die Agglutination von A(1)-Erythrozyten bei Kontakt mit Anti-A-Serum wesentlich stärker und rascher verläuft. Für die Transfusion ist diese Unterteilung nicht von Bedeutung, da Antigen-Antikörper-Reaktionen zwischen A(1) und A(2) sehr selten auftreten und nur sehr schwach sind (Verteilung: A(1) ≈ 20%, A(2) ≈ 80%);


title: Application of Service Robots for Disinfection in Medical Institutions

text: Service robots are increasingly present in all fields of medicine. This paper presents a review of the service robots in medicine with an emphasis on service robots for disinfection in medical institutions. It is shown and described how more and more disinfectant service robots are contributing to a very simple, fast and effective disinfection in medical institutions. Work of the service robot with all necessary components for its function as well as its good and bad sides are in details elaborated and clarified. The aim is to demonstrate the application and use these service robots in medical institutions. Use of these service robots reduces the risk of infection, cost of traditional cleaning and disinfection, and most importantly acquires confidence and security in medical facilities.


title: Perspectives on Global Public Health Informatics

text: Public health professionals’ functions are rapidly expanding beyond their countries’ borders. Many academic centers are recognizing the importance of global health and are creating programs to train students to meet this growing demand. Global health centers and institutes also are being created to focus on the research and programmatic efforts needed to understand the burden of disease worldwide, as well as the financial, political, medical, policy, workforce, and infrastructure issues surrounding any solutions. Due to this emerging interest by the public health community, we need to understand where the intersection between global health and informatics occurs. For many years, the promise of what technology can do to alleviate suffering and support disease surveillance and other public health activities took precedence over understanding the environment in which the technology has to function. People and their participation in the implementation of the technological solution are critical for success. In resource-poor environments, the deployment of technological solutions faces other challenges for success. Lack of stable electrical power, availability of Internet connections, and a workforce that can support the information technology remain barriers to successful implementation. Yet, through experiences in the implementation of information technology as supported by international donors and the US President’s Emergency Plan for AIDS Relief, lessons are being learned to move forward towards the benefits that global health informatics can bring.


title: Posttransplant Complications and Comorbidities

text: Infectious complications cause significant acute morbidity and mortality after pediatric lung transplantation. With the lung graft in direct communication with the environment, it is susceptible to a variety of bacterial, fungal, and viral pathogens. Appreciation for pretransplant risk factors in addition to perioperative and posttransplant exposures is necessary to anticipate, diagnose, and treat infections in this population. Further, epidemiologic associations between infection and chronic allograft dysfunction have been reported and suggest consequences of infectious events may have substantial impact.


title: Expected and Unexpected Effects of Vaccination

text: Vaccination is widely considered to be one of the greatest medical achievements of civilization and one of the top major breakthroughs of humanity.


title: Pulmonology

text: The pleura are composed of two layers, parietal and visceral layers, separated by a pleural space. The parietal pleuron is supplied by systemic vessels and drains into the right atrium via the azygos, hemiazygos, and internal mammary veins. The visceral pleuron is supplied by bronchial and pulmonary vessels and drains into the pulmonary veins.


title: Zoonoses in Cancer Patients

text: Prevention of zoonoses in cancer patients is the theme of this chapter and it is hoped that it will encourage and help doctors caring for such patients to educate them to avoid the infections. Avoidance need not include separation from a pet or occupation or recreation, but the use of caution conditioned by knowledge of the sources of infection and the ways we contact them should lead to effective prevention.


title: Gastroenterology

text: organic—infections, tumors, multiple sclerosis, vestibular nerve or brain stem lesions


title: Beauveria bassiana: Biocontrol Beyond Lepidopteran Pests

text: Beauveria bassiana has been extensively employed since the last century for biocontrol of lepidopteran pests. B. bassiana has also been explored for diverse functions including bioremediation of toxic industrial effluents and heavy-metal polluted soils. Investigations on multifarious applications of chemically diverse secondary metabolites of this entomopathogenic fungus offer promising implications in pharmaceutical and agricultural sectors. In addition, the development of eco-friendly bioremediation strategies using abiotic stress-tolerant strains of B. bassiana will contribute to maintain the sustainability of agroecosystem.


title: Pharmaceutical Intellectual Property Rights in China

text: Recalling the history of China’s pharmaceutical intellectual property right (IPR) protection in the past 20 years, China adopted many international standards for pharmaceutical IPR protection. At the same time, China also issued a series of national regulatory policies to encourage domestic drug innovations (Ding, J Technol Manage Innov 6(2):1–13, 2011) . Therefore, both those policies for incentive innovations and the IPR laws have played important roles in drug development in China. As declared by the 17th National Congress in 2006, China’s national development core strategy has prioritized the adherence to regulatory policies in order to construct a technologically innovative country and the country also wishes to become a global leading country for the implementation of the intellectual properties by 2020 as declared in the “National Intellectual Property Strategy Compendium” by Chinese State Council in 2008. In this chapter, we’ll briefly introduce the basic knowledge of the Chinese IPR system, the key regulatory policies, and the differences between China and western countries. We hope this section for Pharmaceutical Patent Protection may help overseas and multinational pharmaceutical companies gain basic knowledge of IPR, design an optimized IPR protection strategy to best fit their products, and achieve a successful product protection for their intellectual property in China.


title: Abdominalchirurgische Intensivmedizin

text: Die Intensivmedizin in der Allgemeinchirurgie umfasst v. a. die Behandlung akuter Abdominalerkrankungen, wie z. B. der akuten Pankreatitis, gastrointestinaler Blutungen, Ileus und Peritonitis sowie postoperativer Komplikationen bei bauchchirurgischen Eingriffen, wie z. B. Peritonitis, Ileus oder Nachblutungen. Hinzu kommen die postoperative Intensivüberwachung und -behandlung größerer Operationen, bei denen in der Frühphase bestimmte Komplikationen zu erwarten sind. Nicht selten treten zu den spezifischen Risiken allgemeinchirurgischer Eingriffe postoperative Störungen einzelner oder mehrerer Organe hinzu und komplizieren den postoperativen Verlauf.


title: Sessile Innate Immune Cells

text: In this chapter, sessile cells of the innate immune system are briefly introduced. Defined as cells equipped with diverse pattern recognition molecules capable of detecting MAMPs and DAMPs, they encompass cells such as epithelial cells, fibroblasts, vascular cells, chondrocytes, osteoblasts, and adipocytes. Located at the body surfaces, epithelial cells represent the first line of innate immune defense against invading microbial pathogens. They are significant contributors to innate mucosal immunity and generate various antimicrobial defense mechanisms. Also, epithelial cells critically contribute to tissue repair via the phenomenon of re-epithelialization. Fibroblasts operate as classical sentinel cells of the innate immune system dedicated to responding to MAMPs and DAMPs emitted upon any tissue injury. Typically, fibroblasts synthesize most of the extracellular matrix of connective tissues, thereby playing a crucial role in tissue repair processes. Vascular cells of the innate immune system represent an evolutionarily developed first-line defense against any inciting insult hitting the vessel walls from the luminal side including bacteria, viruses, microbial toxins, and chemical noxa such as nicotine. Upon such insults and following recognition of MAMPs and DAMPs, vascular cells react with an innate immune response to create an acute inflammatory milieu in the vessel wall aimed at curing the vascular injury concerned. Chondrocytes, osteoblasts, and osteoclasts represent other vital cells of the skeletal system acting as cells of the innate immune system in its wider sense. These cells mediate injury-promoted DAMP-induced inflammatory and regenerative processes specific for the skeletal systems. Finally, adipocytes are regarded as highly active cells of the innate immune system. As white, brown, and beige adipocytes, they operate as a dynamic metabolic organ that can secrete certain bioactive molecules which have endocrine, paracrine, and autocrine actions.


title: Infantile Viral Illnesses

text: Viruses are the predominant cause of lower respiratory tract illness in infants and a major cause of hospitalization in this vulnerable population. This chapter will review the common respiratory viral agents in infants and young children, including epidemiology and clinical and radiographic features. The role of the laboratory in diagnosis is emphasized with respect to rapid diagnostic techniques and histopathologic features in tissue sections. A brief summary of each of the major infantile respiratory viruses is provided, including respiratory syncytial virus, parainfluenza virus, adenovirus, and influenza virus, as well as the more recently detected and increasingly significant lower respiratory tract viruses, such as human metapneumovirus, coronavirus, rhinovirus, and bocavirus. Congenital and neonatal forms of viral pneumonia, such as cytomegalovirus, herpes simplex virus, and measles virus, are also discussed. Postinfectious complications of viral bronchiolitis are included in this chapter due to the significant persistent morbidity during infancy in many patients.


title: Zoonoses Animal and Human Diseases Endo and Ectoparasites Mainly Mammal I

text: The definition of a zoonosis is that it must affect man but the term is used often outside of medical terminology of animal diseases where man is not involved. Zoonoses are diseases naturally transmitted between animals and man and comprise in total about 80% of all described human infections. Attempts have been made to define different classes of zoonoses according to the man-animal relationship but generally this does not seem to have been accepted. Elton in 1927 stressed the field of wild animal pathology was still virtually untouched, and in 1968 McDiarmid reiterated the view that it remained one of the most neglected aspects of animal ecology. There is now an extensive literature but it is rarely incorporated into ecological texts although disease is often the driving force in population dynamics. The primary driver of infectious disease dynamics is transmission between individuals, yet in most important respects remarkably little is known about the subject (Craft et al. 2008, Haydon 2008). Occasionally, under high population densities, an organism may infect a host outside of its normal range with highly pathogenic effect in its adventitious host.


title: Corticosteroids

text: CORTISOL secretion by the cortex of e adrenal glands (Fig. 32.1) increases in response to any stress in the body, whether physical (such as illness, trauma, surgery or temperature extremes) or psychological. However, this hormone is more than a simple marker of stress levels—it is necessary for the correct functioning of almost every part of the body. Excesses or deficiencies of this crucial hormone also lead to various physical symptoms and disease states [1]. Although cortisol is not essential for life per se, it helps an organism to cope more efficiently with its environment with particular metabolic actions on glucose production and protein and fat catabolism. Nevertheless, loss or profound diminishment of cortisol secretion leads to a state of abnormal metabolism and an inability to deal with stressors, which, if untreated, may be fatal [1, 2].


title: Cell Defence and Survival

text: Central to immune defence mechanisms is the role of transcription factor nuclear factor kappa B (NF-kB). This is a complex biochemical topic with ever more controls revealed. NF-kB determines the production of proinflammatory cytokines and chemokines. Pharmacologists step in with possible means of control. Other systems involved in defence include the cyclooxygenase 2 (Cox-2) enzyme and perioxisome proliferator-activated receptors. Insulin receptor activation needs to be seen in context. The mTOR system directs uptake of nutrients by cells. mTOR is suppressed by rapamycin, whose usage is now quite considerable in the control of transplant rejection.


title: An Innovative Big Data Predictive Analytics Framework over Hybrid Big Data Sources with an Application for Disease Analytics

text: Nowadays, big data are everywhere. Examples of big data include weather data, web-search data, disease reports, as well as epidemic data and statistics. These big data can be easily generated and collected from a wide variety of data sources. A data science framework—such as predictive analytics framework—helps mining data from various big data sources to find useful information and discover knowledge, which can then be transformed into wisdom for appropriate actions. In this paper, we present an innovative big data predictive analytics framework over hybrid big data sources. To demonstrate the effectiveness and practicality of our framework, we conduct several case studies, including one on applying the framework to disease analytics. More specifically, we integrate, incorporate and analyze weather data and web-search data to predict and forecast dengue cases based on a hybrid of three kernels in support vector machine (SVM) ensemble. Results show how our predictive analytics framework benefits health agencies in disease control and prevention.


title: Atomic Force Microscopy: Interaction Forces Measured in Phospholipid Monolayers, Bilayers and Cell Membranes

text: Atomic force microscopy (AFM) is a powerful technique which is commonly used to image surfaces at the nanoscale and single-molecule level, as well as to investigate physical properties of the sample surface using a technique known as force spectroscopy. In this chapter, we review our recent research where we used AFM to investigate physical properties of phospholipid monolayers, bilayers, and cell membranes. We describe the experimental procedures for AFM imaging, force measurements, and theoretical models to analyze force spectroscopy data. The data obtained allowed correlations between AFM topography and local adhesion and mechanoelastic properties of supported lipid bilayers in water, supported pulmonary surfactant films in air, and the plasma membrane of epithelial type II cells. Finally, AFM was applied to help elucidate the effect of anesthetics and cholesterol present in the lipid films.


title: Therapeutic Strategies for DLI: How Should DLI Be Treated?

text: The lungs are vulnerable to toxins because of their large surface area and act as a metabolic site for some substances. Drugs may induce specific respiratory reactions, or the lungs may be affected as part of a generalized response. Drug-induced lung injury (DLI) can involve the airways, lung parenchyma, mediastinum, pleura, pulmonary vasculature, and/or the neuromuscular system. The most common form of DLI is drug-induced interstitial lung disease. There are no disease types specific to DLI, and DLIs are diagnosed on the basis of clinical findings, chest CT images, and histopathologic findings. The first principle of management of DLI is early detection and cessation of treatment with the suspected drug. Response to corticosteroid therapy depends on the histopathologic pattern of drug-induced interstitial lung disease. Prognosis depends on the specific drug and underlying clinical, physiologic, and pathologic severity of lung disease. To minimize DLI morbidity and mortality, all health-care providers should be familiar with the possible adverse effects of medications they prescribe. Individual variability in drug response is an important concern in clinical practice and drug development. Such variability is multifactorial and includes extrinsic factors such as environmental features and genetic and intrinsic factors that affect the pharmacokinetics and pharmacodynamics of drugs.


title: Vaccines Against Viral Infections

text: Vaccines are one of the miracles of modern medicine. Without vaccines, the population—particularly children—would be troubled with multitudinous infectious diseases such as diphtheria, scarlet fever, whooping cough, and measles, just to name a few. Vaccines are available against both viral and bacterial infections; they have saved millions of lives and continue to do so. The World Health Organization hopes to have vaccinated all children under a year old against most infectious diseases by 2020. The history of the public’s acceptance of vaccines has been a stormy one. Anti-vaccination movements have been active since the creation or development of the smallpox vaccine in the eighteenth century and in government-mandated vaccination until the present. An example of this is the fabricated information spread about the relationship between measles vaccine and autism. A successful polio vaccine was developed in the 1950s thanks to the research of three groups, led by Koprowski, Salk and Sabin, although each of these vaccines has its advantages and disadvantages. An oral vaccine has the advantage of ease of administration and a herd effect. Polio vaccine workers have become targets of extremists in Nigeria and Pakistan. Recently, recombinant DNA technology, was used to develop new vaccines in order to avoid the side effects, since live virus is not involved. The future may see the production of vaccines in edible plants, allowing for cheap production and ease in worldwide distribution.


Sequential stages of clinical trials and overview of issues to be considered


title: Emerging and Enabling Technologies in Biodefense

text: The emergence of new biotechnologies provides great promise for biodefense, especially for key objectives of biosurveillance and early warning, microbial forensics, risk and threat assessment, horizon scanning in biotechnology, and medical countermeasure (MCM) development, scale-up, and delivery. Understanding and leveraging the newly developed capabilities afforded by emerging biotechnologies require knowledge about cutting-edge research and its real or proposed application(s), the process through which biotechnologies advance, and the educational and research infrastructure that promotes multi-disciplinary science. Innovation in research and technology development are driven by sector-specific needs and the convergence of the physical, chemical, material, computer, engineering, and/or life sciences. Biotechnologies developed for other sectors could be applied to biodefense, especially if the individuals involved are able to innovate in concept design and development. Of all biodefense objectives, biosurveillance seems to have reaped the most benefit from emerging biotechnologies, specifically the integration and analysis of diverse clinical, biological, demographic, and other relevant data. More recently, scientists have begun applying synthetic biology, genomics, and microfluidics to the development of new products and platforms for MCMs. Unlike these objectives, investments in microbial forensics have been few, limiting its ability to harness biotechnology advances for collecting and analyzing data. Looking to the future, emerging biotechnologies can provide new opportunities for enhancing biodefense by addressing capability gaps.


title: Biodiversity and the Ecology of Emerging Infectious Diseases

text: The question of how biodiversity influences the emergence of infectious diseases is the subject of ongoing research. A set of nonlinear differential equations is been used to explore the interactions between ecology and epidemiology. The model allows for frequency-dependent transmission of infection within host species, and density-dependent transmission between species, via the environment or a vector. Three examples are discussed. It is shown that removing a pathogen may increase a consumer population, decreasing its resource. It is then shown that the presence of a pathogen could enable a predator and a prey species to coexist. Finally the dilution effect, by which increasing biodiversity reduces the transmission of an infectious disease, is investigated.


title: Cervical: Lymphadenopathy

text: The neck region contains around 300 lymph nodes (LNs) out of 800 LNs in the whole body. The detailed study of LNs by Rouviere in 1932 [1] and the later illustration of metastatic predilection of head and neck malignancies to certain LN regions by Lindberg et al. [2] paved the road to a clinically sound classification. The American Academy of Otolaryngology and Head and Neck Surgery (AAO-HNS) and the American Joint Committee on Cancer (AJCC) developed the currently widely accepted levels classification of the cervical LNs (Table 8.1, Figs. 8.1 and 8.2).


title: Quantitative Reverse Transcriptase Polymerase Chain Reaction

text: Since the first documentation of real-time polymerase chain reaction (PCR),(1) it has been used for an increasing and diverse number of applications, including mRNA expression studies, DNA copy number measurements in genomic or viral DNAs,(2–7) allelic discrimination assays,(8,9) expression analysis of specific splice variants of genes(10–13) and gene expression in paraffin-embedded tissues,(14,15) and laser captured microdissected cells.(13,16–19) Therefore, quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) is now essential in molecular diagnostics to quantitatively assess the level of RNA or DNA in a given specimen. QRT-PCR enables the detection and quantification of very small amounts of DNA, cDNA, or RNA, even down to a single copy. It is based on the detection of fluorescence produced by reporter probes, which varies with reaction cycle number. Only during the exponential phase of the conventional PCR reaction is it possible to extrapolate back in order to determine the quantity of initial template sequence. The “real-time” nature of this technology pertains to the constant monitoring of fluorescence from specially designed reporter probes during each cycle. Due to inhibitors of the polymerase reaction found with the template, reagent limitation or accumulation of pyrophosphate molecules, the PCR reaction eventually ceases to generate template at an exponential rate (i.e., the plateau phase), making the end point quantitation of PCR products unreliable in all but the exponential phase.


title: Food Security: Microbiological and Chemical Risks

text: Food Security within a health security context relates to systems dealing with the prevention and control of not only acute but also sporadic and chronic foodborne diseases. The description of food security and safety systems in this chapter will hence include oversight of both microbiological and chemical hazards, which both can cause acute as well as chronic disease events. The Chapter includes a description of existing national and international surveillance systems for foodborne diseases and regulatory systems enabling risk mitigation action for both chemical and microbiological hazards, with specific inclusion of the concerning increase in antimicrobial resistance (AMR) of foodborne microorganisms also related to the animal production systems. The Chapter also includes descriptions of methodology for the quantitative assessment of sustainability of food production systems.


title: Coronaviren

text: Man unterscheidet 5 humanpathogene Coronaviren, die entweder zum Genus Alpha-Coronavirus oder zum Genus Beta-Coronavirus gehören (Subfamilie Coronavirinae, Familie Coronaviridae). Humane Coronaviren (◘ Tab. 58.1) verursachen akute Erkrankungen des oberen Respirationstraktes, die meist problemlos verlaufen, jedoch gelegentlich zu schweren Pneumonien führen. Eine ursächliche Beteiligung an Gastroenteritiden ist möglich, spielt jedoch klinisch und zahlenmäßig keine große Rolle. Zahlreiche animale Coronaviren sind vor allem an respiratorischen und gastrointestinalen Erkrankungen von Säugetieren und Vögeln beteiligt (◘ Tab. 58.1).


title: Cell Regeneration in Lung Injury

text: The acute respiratory distress syndrome (ARDS) is a lethal inflammatory disorder of the lung. Its incidence is estimated at 75 cases per 100,000 population and appears to be increasing [1]. Even with optimal treatment, mortality is about 30% [1–3]. As such, ARDS represents a major public health problem. The effects of two recent crises created by unusual viral infections of the respiratory tract — the severe acute respiratory syndrome (SARS) epidemic caused by the novel SARS coronavirus [4], [5] and the bird flu [6] highlight the importance of research into ARDS. Both viruses cause an ARDS-like picture. Because lung repair and regeneration contribute substantially to the pathophysiology of ARDS, understanding these processes is essential [7]. This chapter focuses on specific cell populations and markers involved in cell division and regeneration. In addition, a brief review of two pathways intimately associated with cell division is provided because of their potential for pharmacologic manipulation.


title: Kawasaki Disease

text: Kawasaki disease is an acute systemic vasculitis syndrome in infants and young children of unknown etiology, which mainly affects small and medium-sized arteries, particularly the coronary artery. Clinical features include an acute febrile illness associated with mucocutaneous involvements and lymphadenopathy. The coronary aneurysms develop in about 10% to 20% of patients, some of which may cause myocardial infarction or lead to ischemic heart disease. Combinations of high-dose gamma globulin and aspirin are the essential treatments for acute Kawasaki disease patients. Bypass surgery and the catheter intervention are the optional treatments for the coronary artery sequelae of Kawasaki disease. Some patients with coronary artery sequelae may develop into adult coronary artery disease.


title: Changing Resource-Based Manufacturing Industry: The Case of the Rubber Industry in Malaysia and Thailand

text: This chapter explores the development potential of the rubber industry in Malaysia and Thailand, which have been leaders in the production of natural rubber (NR) since the 20th century. The analysis of NR producing (upstream segment), processing (midstream segment) and rubber-based manufacturing (downstream segment) in Malaysia and Thailand will find the different timing and sectoral composition in the development of the rubber sector of two countries. It will become clear that in spite of such differences, the two countries share a development pattern in one important respect: The public sector played a crucial role in the development of the upstream segment, while the successful development of the downstream segment largely depends on innovative activities of private entrepreneurs to explore niche international markets for specialized rubber products.


title: The Role of Informal Digital Surveillance Systems Before, During and After Infectious Disease Outbreaks: A Critical Analysis

text: Background One of the main limitations of traditional surveillance systems for disease detection is their inability to detect epidemics in real-time. In addition to syndromic surveillance, a number of informal digital resources have been developed. These systems are based on data collected through media sources such as news reports on the Internet, mailing lists, and RSS (Really Simple Syndication) feeds. The role of such systems at all stages of the epidemic remains unclear. Methods A literature review was carried out on informal digital resources for infectious disease surveillance. We examined the source of information, the manner in which they process and disseminate the information, their role in each phase of disease outbreaks, and whether and to what extent these systems are capable of early detection and management of infectious disease epidemics. Results Informal digital resources use similar sources of data for surveillance. However, they use different algorithms to create their output, and cover different geographic areas. In this regard, they complement each other with respect to information completeness. There is evidence in the literature on the systems’ usefulness in communicating information to public health professionals, as well as to the general public during and after previous epidemics. Retrospective studies of some systems have shown a theoretical decrease in the time of epidemic detection compared to conventional surveillance. However, there is no evidence of the ability for real-time detection. Conclusions Currently, there is little prospective evidence that existing informal systems are capable of real-time early detection of disease outbreaks. Most systems accumulate large amounts of information on a wide variety of diseases, making it difficult to extract critical information. Presenting critical information clearly and precisely remains a challenge.


title: Extracorporeal Membrane Oxygenation in the Treatment of Novel Influenza Virus Infection: A Multicentric Hospital-Based Health Technology Assessment in Lombardy Region

text: ECMO or Extracorporeal Membrane Oxygenation is a specialized heart-lung bypass machine used to take over the body’s heart and lung function while the body heals from injury or illness. One of the disturbing hallmarks of the novel A/H1N1 flu virus is that it produces severe lung damage resulting in ARDS (Acute Respiratory Distress Syndrome). Normally, patients with ARDS are placed on mechanical ventilation in Intensive Care Units (ICUs) and treated with a variety of pharmacological agents to reduce infection and lung inflammation. With A/H1N1 viral pneumonia, mechanical ventilation often does not result in adequate oxygenation so with ECMO the burden of pumping and oxygenating the blood is taken from the heart and lungs, and they are given time to heal. San Matteo Polyclinic Hospital was nominated by the Lombardy Region and the Ministry of Health as national reference for the installation of ECMO to deal severe heart failure and pulmonary caused by novel A/H1N1 flu virus. Clinical Engineering Department of the hospital had a fundamental coordination role in biomedical technology-related issues. It supported high-level management decisions (strategy, management, planning, procurement and maintenance) to answer to Lombardy’s guidelines about the organization of ECMO machines in the region. Moreover it had an important role in the assessment, by the use of HTA procedures, of ECMO alternative technologies.


title: Rituximab-Related Pulmonary Toxicity

text: We report the case of an 80-year-old man treated for follicular grade 3B non-Hodgkin’s lymphoma (NHL). Immunochemotherapy consisted of rituximab (375 mg/m(2)) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) every 21 days. Since the patient complained of mild dyspnea on effort with bilateral basilar crackles audible on auscultation, PET-CT was performed and showed disappearance of the initial 18F-FDG uptake, but new abnormal sites of 18F-FDG uptake were evident in the sub-pleural areas of the lung, mostly on the right side. After starting the fifth cycle of rituximab-CHOP, the dyspnea worsened. Chest-X ray and HRCT were consistent with an interstitial infiltration, including sub-pleural air-space consolidation, and “ground-glass” opacities, small pulmonary cysts and thickening of the interlobular septa were also seen. Trans-bronchial biopsy was performed and revealed interstitial inflammation of the lung parenchyma, as well as swelling and hyperplasia of atypical type II alveolar cells. Alternative diagnoses than drug-related pulmonary toxicity are discussed, and a literature review is provided.


title: Krankheitsbilder

text: Das Spektrum der pneumologischen Krankheitsbilder ist groß und oft fächerübergreifend. Neben den häufigsten Erkrankungen wie COPD, Asthma bronchiale oder Tumoren des Thorax werden hier weitere häufige und seltene Erkrankungen dargestellt, die im Alltag das Bild einer pneumologischen Station prägen. Die führende Symptomatik, der diagnostische Weg und auch therapeutische Vorgehensweisen werden verständlich erörtert, um so den Umgang mit pneumologischen Erkrankungsbildern zu erleichtern.


title: Pulmonary Hypertension in an Oncologic Intensive Care Unit

text: Pulmonary hypertension (PH) is the condition of elevated pressures in the pulmonary circulation. PH can develop acutely in patients with critical illness such as acute respiratory distress syndrome, sepsis, massive pulmonary embolism, left ventricular dysfunction, or after surgery. In a cancer patient, unique etiologies such as myeloproliferative disorders, tyrosine kinase inhibitors, or tumor emboli may result in PH. Early recognition and treatment of the causative condition may reverse acute PH or return chronic PH to its baseline status. Progression of the disease or its decompensation due to infection, a thromboembolic event, or other triggers can lead to admission to an intensive care unit. Regardless of etiology, the development or worsening of PH may precipitate hypoxemia, hemodynamic instability, or right ventricular failure, which can be challenging to manage or even fatal. In select cases, rapid institution of advanced treatment modalities may be warranted. This chapter reviews the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and prognosis of PH and presents a comprehensive analysis of PH and right heart failure management strategies in the critical care setting. In particular, a unique perspective on oncologically relevant PH is provided.


title: Bakterielle Infektionen

text: Vor der Einführung von Antibiotika führten schwere bakterielle Infektionen wie Sepsis, Diphtherie und Meningitis fast zwangsläufig zum Tod. Heute meist folgenlose Erkrankungen wie Typhus, Scharlach oder bakterielle Gelenksinfektionen führten früher zu Tod oder schweren Behinderungen. Gefahren gehen heute v. a. durch Resistenzentwicklungen gegen Antibiotika (z. B. bei der Tuberkulose) und durch mangelnde Impffreudigkeit (z. B. bei Diphtherie) aus. So sind bakterielle Infektionen weiterhin nicht zu verharmlosen.


title: DNA Damaging Drugs

text: The classical anti-cancer agents comprise cytotoxic compounds. Mostly, these drugs act by exerting DNA damage. In essence, there are two major response phenotypes available to a cell upon DNA damage, such as a chemotherapeutic drug action, to arrest the cell cycle and repair the damage, to initiate a pathway to apoptosis (programmed cell death).


title: Adeno-Viren

text: Adeno-Viren erzeugen akute Erkältungskrankheiten, Konjunktivitis, Keratitis, Meningitis, Zystitis und Gastroenteritis. Sie wirken immunmodulatorisch und persistieren lange Jahre in den Tonsillen und können bei Immundefekten reaktiviert werden. Das Virus wurde erstmals 1953 in Explantaten von Tonslllengewebe anhand seines zytopathischen Effekts in vitro nachgewiesen. 1956 erhielten die Isolate die Bezeichnung “Adeno-Viren„ (Tonsillen = adenoides Gewebe). Der Typ 12 war das erste Human-Virus, bei dem man Tumorigenität im Tier beobachtete, beim Menschen gibt es keine entsprechenden Hinweise.


title: Advances in Molecular Diagnostic Approaches for Biothreat Agents

text: The advancement in Molecular techniques has been implicated in the development of sophisticated, high-end diagnostic platform and point-of-care (POC) devices for the detection of biothreat agents. Different molecular and immunological approaches such as Immunochromatographic and lateral flow assays, Enzyme-linked Immunosorbent assays (ELISA), Biosensors, Isothermal amplification assays, Nucleic acid amplification tests (NAATs), Next Generation Sequencers (NGS), Microarrays and Microfluidics have been used for a long time as detection strategies of the biothreat agents. In addition, several point of care (POC) devices have been approved by FDA and commercialized in markets. The high-end molecular platforms like NGS and Microarray are time-consuming, costly, and produce huge amount of data. Therefore, the future prospects of molecular based technique should focus on developing quick, user-friendly, cost-effective and portable devices against biological attacks and surveillance programs.


title: Antimicrobial Use in Surgical Intensive Care

text: Judicious antimicrobial use is essential in modern surgical intensive care. This requires careful clinical assessment and aggressive diagnostics to identify sources of infection as well as their noninfectious mimics. Because antimicrobial agents affect the ecology of resistant organisms in neighboring patients and the wider environment, as well as cause other common adverse effects, restrained initiation of antibiotics may be as valuable among hemodynamically stable patients with possible infection as is urgent empiric coverage in those threatening septic shock. Early collaboration with infectious disease and pharmacy consultants yields more appropriate treatment and improved morbidity, duration of hospital care, costs, and survival.


title: Infection Prevention and Control: A Biodefense Measure

text: Infection prevention and control (IPC) is the foundation for preventing the spread of infectious diseases, regardless of source, during medical treatment. Biological attacks will inevitably involve the medical management of sick individuals, which will not only tax the healthcare system, but also highlight the vital importance of infection control. Reducing the capacity for disease transmission will be pivotal in not only the early stages of an outbreak or biological attack, but also during times of crisis. Infection control programs also conduct disease surveillance and reporting to public health departments, which is crucial during an attack or outbreak. Infection control failures, like those in the 2013–2016 Ebola virus disease outbreak and continued Middle East respiratory syndrome (MERS) outbreaks, act as amplifiers for pathogen transmission. In the event of a biological attack, the strength and stamina of a hospital’s infection control program will be critical to early recognition, isolation, treatment, and reducing the spread of infection.


title: China Declares Global State of Emergency: An Urgent Telegram from Taihu

text: May 18th, 2013, China’s 4th most powerful politician, Yu Zhengsheng, Chairman of the National Committee of the CPPCC (Chinese People’s Political Consultative Conference) opened the Second Conference of the (carbon-neutralized) Taihu World Cultural Forum in Hangzhou, a city 1 h by speed train southwest of Shanghai. “What kind of a planet will we leave to our descendants? This is an urgent subject which deserves the collective attention of the whole world,” he said with a sincere air of emergency.


title: Disaster Response Policy Change in the Wake of Major Disasters, Labeled Focusing Events

text: Responding to the will of the people or the will of the government after a focusing event is complex and fraught with perils; this is none more so than after a major disaster that has brought on the sudden death of many people or the initial incalculable destruction of property or the environment. Korea has experienced several of these types of focusing events that have had major social and policy implications between the years 1948 and 2015. We analyzed them to glean their impact on disaster response policy, organizational and law reform, and first response and national countermeasures – and presented them in a clear and logical array so that the information could lead to a new type of disaster management model. Additionally, we look at how these focusing events altered the political, policy alternative and problem streams, as well as media coverage and policy change in the wake of the focusing event. And finally, we analyze disaster-triggered policy change in Korea to find out if the relation between the focusing event and institutional reforms for disaster response is path-dependent.


title: Bio-Gefahren und Seuchen

text: Zukunftsvorstellungen basieren gemeinhin auf Utopien, auf nur in der Vorstellung möglichen Szenarien. In diesen kommen haufenweise super-intelligente, metallisch glänzende neuartige Gegenstände, Roboter, fliegende Autos, Raumanzüge und Speisen in Pillenform vor. Es gibt aber auch Schreckensvisionen wie die von der Wiederkehr der Pest, die einst ein Drittel der europäischen Bevölkerung dahinraffte, oder von einer Influenza- Pandemie, wie sie 1918-19 wütete, und die 20 bis 40 Millionen Menschen das Leben kostete.


title: Targeted Delivery of Surface-Modified Nanoparticles: Modulation of Inflammation for Acute Lung Injury

text: Nanocarriers have been widely employed in the diagnosis and treatment of various diseases. The drug release kinetics and pharmacodynamics could be adjusted by changing the materials, designs, and physicochemical properties of the carriers. Furthermore, the carrier surface could be modified to minimize the particle clearance, increase the circulation duration, escape the biological protective mechanisms, penetrate through physical barriers, and prolong the residence of the drug at the target site. Among lung diseases, acute lung injury has been considered life-threatening with approximately 190,000 cases and 74,500 deaths per year in the USA. Numerous researches have reported the efficacy of drug-encapsulated nanoparticles in the treatment of acute lung injury. The use of nanoparticles could help minimize the effect of airway defenses in the lung, thus provides a prolonged retention, sustained drug release, and targeted delivery to the lung tissues. Meanwhile, the toxicity of nanoparticles in the lungs needs to be investigated thoroughly to alleviate the safety concerns. In this chapter, we discuss the targeted pulmonary delivery of surface-modified nanocarriers to efficiently treat acute lung injury.


docid: lvwcdnaa

title: Gastrointestinal Infections

text: Establishing a specific etiology for gastrointestinal infections can be challenging because of the common clinical features and wide variety of causative microorganisms. In many cases, the etiologic agent cannot be determined using traditional diagnostic methods and may result in unnecessary antibiotic use or prolonged periods of illness. Molecular tests provide many advantages over traditional laboratory methods but, with the exception of a few analytes, are still largely in the developmental phase for gastrointestinal pathogens and are not widely used. The main advantages of molecular tests include increased sensitivity and the ability to detect agents which will not grow in culture. To test for all possible gastrointestinal pathogens at one time would require a large panel that would include a variety of bacterial, viral and parasitic agents. Challenges inherent in developing diagnostic molecular panels include ensuring that all variants of a particular microorganism can be detected as well as the rapid evolution of pathogens. In this chapter, the diagnostic merit of molecular tests as well as available tests will be presented for the major groups of gastrointestinal pathogens.


title: The Indonesian Construction Industry

text: This chapter describes an overview of the Indonesian construction industry. It starts with introducing a general profile of the country, its location, demography, form of state and legal system, and its economic performance. This section is then followed by an overview of the Indonesian construction industry. It describes the industry’s activities, contribution to the national’s economic growth, its stakeholders and support infrastructure, regulations and management systems, latest developments and lessons learned. The third section is a description about Indonesian construction firms, which focuses on the contractors and their business activities. The last section of this chapter links the Indonesian contractors with the background of this study, which is a review of the crises faced by the Indonesian contractors.


title: Antiviral Host Defence Peptides

text: The ongoing global mortality and morbidity associated with viral pathogens highlights the need for the continued development of effective, novel antiviral molecules. The antiviral activity of cationic host defence peptides is of significant interest as novel therapeutics for treating viral infection and predominantly due to their broad spectrum antiviral activity. These peptides also display powerful immunomodulatory activity and are key mediators of inflammation. Therefore, they offer a significant opportunity to inform the development of novel therapeutics for treating viral infections by either directly targeting the pathogen or by enhancing the innate immune response. In this chapter, we review the antiviral activity of cathelicidins and defensins, and examine the potential for these peptides to be used as novel antiviral agents.


title: Emerging and Transboundary Animal Viral Diseases: Perspectives and Preparedness

text: The epidemics and pandemics of a few infectious diseases during the past couple of decades have accentuated the significance of emerging infectious diseases (EIDs) due to their influence on public health. Although Asia region has been identified as the epicentre of many EIDs and upcoming infections, several new pathogens have also emerged in the past in other parts of the world. Furthermore, the emergence of new viral diseases/infections, such as Rift Valley fever, West Nile fever, SARS coronavirus, Hendra virus, avian influenza A (H5N1), Nipah virus, Zika virus and swine influenza A (H1N1) virus, from time to time is a glaring example threatening adversely both animal and public health globally. Infectious diseases are dynamic and concerning due to their epidemiology and aetiological agents, which is manifested within a host, pathogen and environment continuum involving domestic animals, wildlife and human populations. The complex relationship among host populations and other environmental factors creates conditions for the emergence of diseases. The factors driving the emergence of different emerging infectious disease (EID) interfaces include global travel, urbanisation and biomedical manipulations for human EIDs; agricultural intensification for domestic animal EIDs; translocation for wildlife EIDs; human encroachment, ex situ contact and ecological manipulation for wildlife–human EIDs; encroachment, new introductions and ‘spill-over’ and ‘spill-back’; and technology and industry for domestic animal–human EIDs. The concepts of sanitary and phytosanitary (SPS) measures and biosecurity have gained recognition globally in almost all the realms of human activities, including livestock health and production management. This chapter provides the experience gained in the control and management of a few important TADs and EIDs along with the successes, constraints, limitations and future research needs for developing better control approaches.


title: Natural Virucidal Compounds in Foods

text: Many plant essential oils, extracts, and individual chemical components have been demonstrated to possess antiviral efficacy against enveloped and/or non-enveloped viruses. In general, plant antimicrobials exhibit greater antiviral efficacy against enveloped viruses than non-enveloped viruses (though not in all cases). There appear to be multiple mechanisms of antiviral action for plant antimicrobials; nevertheless, the majority of antimicrobials appear to act either directly on the virus itself (e.g., on the envelope or capsid) or during the early stages of virus replication following internalization of the virus into its host cell.


title: Fuzzy Decision Making in Public Health Strategies

text: Making decision is one of the most fundamental activities of human beings (Klir & Yuan, 1995; Yager & Filev, 1994; Zadeh, 1973). This is particularly true in Public Health where decisions usually have relevance for millions of people. In the field of vaccination strategies design, decision making concerning the target population for the immunization program, the proportion of susceptibles to be vaccinated, the optimal age to immunize children and the nature of the strategy, e.g. selective or indiscriminate, are examples of the variables to be optimized, subject to a set of constraints. As an example, we present in this chapter a fuzzy model to decision making applied to the design of the vaccination campaign against measles in São Paulo, Brazil (Massad et al., 1999)


title: Disasters as Extreme Events and the Importance of Network Interactions for Disaster Response Management

text: We discuss why disasters occur more frequently and are more serious than expected according to a normal distribution. Moreover, we investigate the interaction networks responsible for the cascade-like spreading of disasters. Such causality networks allow one to estimate the development of disasters with time, to give hints about when to take certain actions, to assess the suitability of alternative measures of emergency management, and to anticipate their side effects. Finally, we identify other fields where network theory could help to improve disaster response management.


title: Influenzavirus A/H1N1/2009 – ein Überblick vom Ausbruch bis zur Vakzination

text: Influenzaepidemien und Influenzapandemien treten immer wieder auf, unterscheiden sich aber deutlich im Schwergrad der klinischen Symptome. Ein Beispiel hierfür ist der Ausbruch von Influenza A/H1N1/2009, der im April 2009 in Mexiko und Kalifornien beschrieben wurde und vermutlich schon einige Wochen zuvor aufgetreten war. Dieses Virus ist genetisch nicht näher mit der zirkulierenden saisonalen Influenza aber mit zirkulierenden Schweineviren verwandt. Der neue Virusstamm ist eine Reassortante zwischen zwei verschiedenen Virusstämmen, die bei Schweinen vorkommen, und kann nun auch von Mensch zu Mensch übertragen werden. Entsprechend den Leitlinien der WHO handelt es sich um ein pandemisches Virus, bis Juli 2010 wurden weltweit insgesamt ca. 18.000 Todesfälle gemeldet.


title: Infektionskrankheiten

text: Erreger. Morbilli-Virus, ein RNA-Virus aus der Familie der Paramyxoviren.


docid: usxkyiuw

title: Isolation Precautions for Visitors to Healthcare Settings

text: Visitors may be involved in infection transmission within healthcare settings; however, there is currently limited published data on this subject. This chapter describes situations in which visitor-associated infection transmission occurred and highlights the potential role of visitors in the transmission of pathogenic organisms that can lead to outbreaks in healthcare settings. Infection prevention measures, including isolation precautions and visitor restriction, may be utilized and potentially adapted in order to protect patients and their visitors as well as healthcare personnel. The practical and ethical challenges regarding the use of isolation precautions among visitors to healthcare facilities are discussed.


title: Adult Still’s Disease

text: 1. The clinical features of adult Still’s disease resemble the systemic form of JRA a. Seronegative chronic polyarthritis associated with a systemic inflammatory illness b. Initially described in 1897 by George F. Still (pathologist) c. Subsequently detailed in adults in 1971 by Eric Bywaters 2. Epidemiology a. Rare b. Affects both genders equally c. Exists worldwide d. Majority present at age 16–35 years i. 75% before age 35


title: Adverse Drug Reactions

text: Adverse events and adverse drug reactions are common in clinical practice. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from several medications to treat infections, other medical conditions, and in the clinical setting of oncologic treatment. The objective of this chapter to review current data on adverse drug reactions, here classified as (i) severe adverse drug reactions, (ii) uncomplicated cutaneous adverse drug reactions, and (iii) adverse drug reactions caused by chemotherapy drugs, particularly those cases whereby the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. We describe aspects associated with these events, presenting a detailed analysis of each of them.


title: Special Engineering Aspects

text: The specific characteristics of mammalian cells discussed in Chap. 2 require adapted solutions for bioreactor design and operation. Especially, cell damage by shear stress and aeration has to be considered. Therefore this chapter starts with a detailed discussion of shear stress effects on mammalian cells (anchorage-dependent and suspendable cells) in model systems and bioreactors, respectively, and consequences for reactor design. Appropriate oxygen supply is another critical issue, as adapted oxygen supply systems are required. Techniques for immobilization of cells, either grown on microcarriers in suspension culture or within macroporous carriers in fixed bed or fluidized bed reactors, are discussed as well. With respect to the operation of bioreactors, the characteristics of different culture modes (batch, fed-batch, chemostat, perfusion) are introduced and practical examples are given. Finally, concepts for monitoring of bioreactors, including offline and online methods as well as control loops (e.g. O(2), pH), are considered.


title: Clinical Management of Patients Infected with Highly Pathogenic Microorganisms

text: The clinical management of high consequence infectious diseases (HCID) poses an immense challenge, seen largely varying standards in terms of infection prevention control (IPC) as well as in quality of clinical care. This chapter gives an overview of possible treatment as well as IPC options. Lessons learned within the German Permanent Working Group of Competence and Treatment Centres for highly infectious, life-threatening diseases (STAKOB) are taken into account.


title: Spezielle Erreger und Infektionen

text: MRE, MRSA, VRE und andere Erreger bis hin zu den viralen hämorrhagischen Fiebererregern erfordern spezielle Risikoanalysen und risikoadaptierte Maßnahmen. Dieses Kapitel fasst die Empfehlungen zusammen und gibt tabellarische Übersichten, was wann zu tun ist.


title: Major Advances in the Development of Synthetic Oligosaccharide-Based Vaccines

text: Because of their involvement in a variety of different biological processes and their occurrence onto pathogens and malignant cell surface, carbohydrates have been identified as ideal candidates for vaccine formulation. However, as free oligosaccharides are poorly immunogenic and do not induce immunological memory in the most at risk population (infants and young children, elderly and immunocompromised patients), glycoconjugate vaccines containing the same carbohydrate antigen covalently linked to an immunogenic carrier protein have gained a prominent role. Accordingly, a number of glycoconjugate vaccines mostly directed against infections caused by bacterial pathogens have been licensed and are currently available on the market. However, also glycoconjugate vaccines suffer from significant drawbacks. The challenging procedures required for the isolation and purification of the carbohydrate antigen from its natural source often lead to poor homogeneity and presence of biological contaminants, resulting in batch-to-batch variability. Moreover, in some cases, the overwhelming immunogenicity of the carrier protein may induce the carbohydrate epitope suppression, causing hyporesponsiveness. The development of synthetic oligosaccharide-based vaccine candidates, characterized by the presence of pure and well-defined synthetic oligosaccharide structures, is expected to meet the requirement of homogeneous and highly reproducible preparations. In the present chapter, we report on the major advances in the development of synthetic carbohydrate-based vaccines. First of all, we describe different strategies developed during the last years to circumvent the inherent difficulties of classical oligosaccharide synthesis, such as the one-pot glycosylation and the solid-phase synthesis, and their application to the preparation of carbohydrate antigens apt to conjugation with protein carriers. Next, we discuss the most representative methodologies employed for the chemical ligation of oligosaccharide structures to proteins. Finally, in the last section, we report significant examples of fully synthetic vaccines exploiting the multivalency effect. These constructs are based on the concept that the conjugation of multiple copies of synthetic oligosaccharide antigens to multivalent scaffolds, such as dendrimers, (cyclo)peptides, gold nanoparticles, and calixarenes, raises cooperative interactions between carbohydrates and immune receptors, leading to strong enhancement of the saccharide antigen immunogenicity.


title: Study on the Law of Diffusion of Sudden Pollutants in Subway Ventilation Shaft

text: The underground subway stations have become the targets of terrorism due to the features of staff-intensive and poor ventilation. In the present study, the dynamic mesh model was used to predict the dynamic change of the flow field in the tunnel induced by the train motion. The DPM model was employed to simulate the interaction between the continuous phase of the air and the discrete phase of pollution particles. Accordingly, the dispersion of sudden pollutants released in the ventilation shaft was investigated. The results show that the submicron particles have a good following performance with the air. The dispersion characteristics of the particles highly depend on the unsteady flow field in the tunnel, which is significantly affected by the piston effect induced by the train motion. It can be concluded that particle diffusion experiences three stages: vertical forward and reverse diffusion in the wind shaft, vertical positive diffusion in the wind shaft, and longitudinal stable diffusion in the interval tunnel. It hopes that the study can provide guides for future biochemical protection in the subway system.


docid: rrmhnhfk

title: Migration of NK cells

text: NK cells were initially thought to be endowed with a particular migratory pattern and to mainly circulate in the blood. The recent findings reviewed here highlight that NK cells can exhibit different predilictions for tissue compartments, i.e., lymph nodes, inflamed tissues, etc., where they can play an important role as active participants in directing DC maturation and T cell response polarization and/or as cytotoxic effector cells. The mechanisms regulating tissue-selective NK cell homing and functional specialization are just starting to be unraveled, but the importance of tissue microenvironment is becoming increasingly clear. An example is given by decidual NK cells whose differentiation, accumulation and functional program are under hormonal influence.


title: Infektionen

text: Trotz Weiterentwicklung moderner Antibiotika in den letzten Jahren sind die Letalitätszahlen der bakteriellen (eitrigen) Meningitis weiterhin hoch; Überlebende haben häufig neurologische Residuen. Die ungünstigen klinischen Verläufe der bakteriellen Meningitis sind meist Folge intrakranieller Komplikationen, wie z. B. eines generalisierten Hirnödems, einer zerebrovaskulären arteriellen oder venösen Beteiligung oder eines Hydrozephalus.


title: Koorts bij volwassenen

text: Koorts wordt bij niet-immuungecompromitteerde volwassenen in de eerste lijn zonder recent verblijf in het buitenland meestal veroorzaakt door een luchtweginfectie. Bij ouderen vormen urineweginfecties een relatief frequente oorzaak van koorts. Bij ontbreken van richtinggevende voorgeschiedenis, klachten of verschijnselen volstaat men in eerste instantie met lichamelijk onderzoek van KNO-gebied en longen. Bij negatieve bevindingen volgt urineonderzoek. Wanneer geen afwijkingen gevonden worden, gaat men uit van een onschuldige virale oorzaak. Bij een ernstig zieke indruk of verminderd bewustzijn is het lichamelijk onderzoek allereerst gericht op eventuele stoornissen in de vitale functies, omdat deze onmiddellijke therapeutische implicaties hebben. Als de koorts een week aanhoudt of eerder bij verandering van het beeld, dient een uitgebreide anamnese en algemeen lichamelijk onderzoek plaats te vinden om diagnostische aanknopingspunten op te sporen. Ook kan de arts dan aanvullend onderzoek laten verrichten: in eerste instantie bloed-, urine- en fecesonderzoek en een X-thorax, eventueel gevolgd door X-sinussen en een mantoux-reactie. Medicatie wordt zo veel mogelijk gestaakt om een allergie aan te tonen of uit te sluiten. Na enkele dagen herhaalt men anamnese en lichamelijk onderzoek. Twee weken onbegrepen koorts is reden voor verdere (poli)klinische evaluatie. Concrete aanwijzingen op grond van steeds herhaalde anamnese en lichamelijk onderzoek zijn richtinggevend voor de inzet van complex aanvullend onderzoek. Dit bestaat onder meer uit bloedkweken, uitgebreider bloedonderzoek, leverbiopsie, beenmergpunctie en CT-scan buik en thorax. Bij patiënten ouder dan 55 jaar met koorts en een verhoogde bezinking is een biopsie van de arteria temporalis zinvol. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1274-0_5) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.


title: Introduction to Computer Network Vulnerabilities

text: System vulnerabilities are weaknesses in the software or hardware on a server or a client that can be exploited by a determined intruder to gain access to or shut down a network. Donald Pipkin defines system vulnerability as a condition, a weakness of or an absence of security procedure, or technical, physical, or other controls that could be exploited by a threat [1].


title: Plant Virus Diversity and Evolution

text: Historically, the majority of plant virology focused on agricultural systems. Recent efforts have expanded our knowledge of the true diversity of plant viruses by studying those viruses that infect wild, undomesticated plants. Those efforts have provided answers to basic ecological questions regarding viruses in the wild, and insights into evolutionary questions, regarding the origins of viruses. While much work has been done, we have merely scratched the surface of the diversity that is estimated to exist. In this chapter we discuss the state of our knowledge of virus diversity, both in agricultural systems as well as in native wild systems, the border between these two systems and how viruses adapt and move across this border into an artificial, domesticated environment. We look at how this diversity has affected our outlook on viruses as a whole, shifting our past view of viruses as purely antagonistic entities of destruction to one where viruses are in a mutually beneficial relationship with their hosts. Additionally, we discuss the current work that plant virology has put forth regarding the evolutionary mechanisms, the life histories, and the deep evolution of viruses.


title: Phyllospheric Microbiomes: Diversity, Ecological Significance, and Biotechnological Applications

text: The phyllosphere referred to the total aerial plant surfaces (above-ground portions), as habitat for microorganisms. Microorganisms establish compositionally complex communities on the leaf surface. The microbiome of phyllosphere is rich in diversity of bacteria, fungi, actinomycetes, cyanobacteria, and viruses. The diversity, dispersal, and community development on the leaf surface are based on the physiochemistry, environment, and also the immunity of the host plant. A colonization process is an important event where both the microbe and the host plant have been benefited. Microbes commonly established either epiphytic or endophytic mode of life cycle on phyllosphere environment, which helps the host plant and functional communication with the surrounding environment. To the scientific advancement, several molecular techniques like metagenomics and metaproteomics have been used to study and understand the physiology and functional relationship of microbes to the host and its environment. Based on the available information, this chapter describes the basic understanding of microbiome in leaf structure and physiology, microbial interactions, especially bacteria, fungi, and actinomycetes, and their adaptation in the phyllosphere environment. Further, the detailed information related to the importance of the microbiome in phyllosphere to the host plant and their environment has been analyzed. Besides, biopotentials of the phyllosphere microbiome have been reviewed.


title: Polymers in the Delivery of siRNA for the Treatment of Virus Infections

text: Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a ‘‘magic bullet’’, due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by nonspecific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data.


title: Host defenses

text: Repeated episodes of viral upper respiratory tract infections occur anywhere from four to eight times per year in healthy individuals Local and systemic defense mechanisms exist to battle respiratory tract pathogens. Clinical manifestations are mainly due to host inflammatory response. Unfortunately, the host defense mechanisms are very often not sufficient to prevent subsequent/repeated episodes of infections(s). Further insight into the interaction of infectious agent and host immune response, genetic factors, and environmental factors is needed for a better understanding of why humans repeatedly and frequently suffer from infections with respiratory agents and develop a disease syndrome known as common cold.


title: Helix-helix interaction patterns in membrane proteins

text: Membrane-spanning α-helices represent major sites of protein-protein interaction in membrane protein oligomerization and folding. As such, these interactions may be of exquisite specificity. Specificity often rests on a complex interplay of different types of residues forming the helix-helix interfaces via dense packing and different non-covalent forces, including van der Waal’s forces, hydrogen bonding, charge-charge interactions, and aromatic interactions. These interfaces often contain complex residue motifs where the contribution of constituent amino acids depends on the context of the surrounding sequence. Moreover, transmembrane helix-helix interactions are increasingly recognized as being dynamic and dependent on the functional state of a given protein.


title: Acute Respiratory Failure and Management

text: Acute respiratory failure is a common reason for admission to the pediatric intensive care unit in oncology patients. Acute respiratory complications are also common after pediatric hematopoietic stem cell transplant (HSCT), accounting for a high proportion of HSCT-related morbidity and mortality. Evaluation of these patients requires a thorough workup that includes identification and treatment of infectious etiologies, and treatment for noninfectious causes once infectious causes are ruled out. These patients should be closely monitored for development of pediatric acute respiratory distress syndrome (PARDS) with early escalation of respiratory support. Patients undergoing a trial of noninvasive ventilation (NIV) should be continuously monitored to ensure they are responding. Prolonged delay of endotracheal intubation in patients who do not improve or worsen on NIV could worsen their outcome. Optimal treatment of immunocompromised patients with acute lung failure requires early and aggressive lung protective ventilation, prevention of fluid overload, and rapid diagnosis of underlying causes to facilitate prompt disease-directed therapy.


title: Conclusion

text: This chapter provides a summary of the global response to the AIDS pandemic and offers seven valuable lessons that can be learned from its history, which will hopefully be of value to the global community when confronted with future pandemics. These lessons relate to the behavior of donors, the importance of accountability, the need to understand the reality of the UN system, the advantage of a balanced and comprehensive approach to global challenges, and the importance of engaging civil society. The future of the World Health Organization, and its ability to provide leadership in addressing global pandemics and restore its credibility and legitimacy as the world’s leader in global health, is unclear. Hopefully, reforms now underway and the election of a new Director General, Tedros Ghebreyesus will enable this transformation.


title: The Discovery and Early Clinical Evaluation of the HCV NS3/4A Protease Inhibitor Asunaprevir (BMS-650032)

text: The discovery of asunaprevir (1) began with the concept of engaging the small and well-defined S(1)’ pocket of the hepatitis C virus (HCV) NS3/4A protease that was explored in the context of tripeptide carboxylic acid-based inhibitors. A cyclopropyl-acyl sulfonamide moiety was found to be the optimal element at the P(1)-P(1)’ interface enhancing the potency of carboxylic acid-based prototypes by 10- to >100-fold, dependent upon the specific background. Optimization for oral bioavailability identified a 1-substituted isoquinoline-based P(2)* element that conferred a significant exposure advantage in rats compared to the matched 4-substituted quinoline isomer. BMS-605339 (30) was the first cyclopropyl-acyl sulfonamide derivative advanced into clinical trials that demonstrated dose-related reductions in plasma viral RNA in HCV-infected patients. However, 30 was associated with cardiac events observed in a normal healthy volunteer (NHV) and an HCV-infected patient that led to the suspension of the development program. Using a Langendorff rabbit heart model, a limited structure-cardiac liability relationship was quickly established that led to the discovery of 1. This compound, which differs from 30 only by changes in the substitution pattern of the P(2)* isoquinoline heterocycle and the addition of a single chlorine atom to the molecular formula, gave a dose-dependent reduction in plasma viral RNA following oral administration to HCV-infected patients without the burden of the cardiac events that had been observed with 30. A small clinical trial of the combination of 1 with the HCV NS5A inhibitor daclatasvir (2) established for the first time that a chronic genotype 1 (GT-1) HCV infection could be cured by therapy with two direct-acting antiviral agents in the absence of exogenous immune-stimulating agents. Development of the combination of 1 and 2 was initially focused on Japan where the patient population is predominantly infected with GT-1b virus, culminating in marketing approval which was granted on July 4, 2014. In order to broaden therapy to include GT-1a infections, a fixed dose triple combination of 1, 2, and the allosteric NS5B inhibitor beclabuvir (3) was developed, approved by the Japanese health authorities for the treatment of HCV GT-1 infection on December 20, 2016 and marketed as Ximency(®).


title: Fortsetzung des Wandels unter Präsident Mbeki (1999–2009)

text: Sowohl seitens des ANC als auch der SACP, und zwar vor wie nach den Wahlen 1999, wurde die fortdauernde Bedeutung des RDP hervorgehoben und es kam zu einer auch vom COSATU unwidersprochenen und geradezu zelebrierten Neubestätigung bzw. Wiederbestätigung des RDP („reaffirmation of the RDP“) durch die Tripartite Alliance.


title: Nanoparticles as Precious Stones in the Crown of Modern Molecular Biology

text: The interdisciplinary field of research on biosystems at the nanoscale involving physical sciences, molecular engineering, biology, biotechnology, and medicine supplements the knowledge of synthesizing new drugs, targeted delivery, regenerative medicine, and neuromorphic engineering forms the booming research in the present society. The present chapter deals with the role of nanoparticles in modern molecular biology. This is an interesting area of research that creates great impact on the healthcare of the society. The prime focus is to give the reader a historic background of nanomaterial application in biology and medicine. We have also provided the overview of most recent developments in this field leading to discussion of hard road to commercialization.


title: Multi-agents Simulation on Unconventional Emergencies Evolution Mechanism in Public Health

text: Based on the cellular automaton principle and multi-agents theory of complex systems, this essay studied the public health unconventional emergencies generation and evolution mechanism, established evolution model and carried out simulation of the public health unconventional emergencies evolution mechanism, and finally took SARS emergency for an example. Research results showed that the evolution of the public health emergency often promots other linkage emergencies, the damage of linkage system is larger than that of promotion system, and the damage is uncontrolled except for controlling the promotion system effectively, just like isolation measures or inject vaccine for individual of the promotion system so as to prevent promotion system from producing linkage hazards.


title: Regional Innovation Systems Analysis and Evaluation: The Case of the Czech Republic

text: Regional innovation systems (RIS) have become a very important regional policy instrument. This instrument is based on linkages among the region’s institutions from the public and private sector. These linkages are very important because they provide an environment for the innovation process, which is the primary goal of the RIS. In this paper, we have defined and described the main characteristics common to every RIS. Knowledge of these characteristics allows us to create a new method to make it possible to analyze individual RISes. The goal of this chapter is to present a new method for evaluating RISes. The method must by easily applied in order for it to be used practically to map the development of the individual innovative systems in a region. The method is based on evaluating both qualitative and quantitative indicators and on applying WSA methods. The paper presents the application of this method on individual regions in the Czech Republic (NUTS3).


title: Live-Attenuated Bacterial Vectors for Delivery of Mucosal Vaccines, DNA Vaccines, and Cancer Immunotherapy

text: Vaccines save millions of lives each year from various life-threatening infectious diseases, and there are more than 20 vaccines currently licensed for human use worldwide. Moreover, in recent decades immunotherapy has become the mainstream therapy, which highlights the tremendous potential of immune response mediators, including vaccines for prevention and treatment of various forms of cancer. However, despite the tremendous advances in microbiology and immunology, there are several vaccine preventable diseases which still lack effective vaccines. Classically, weakened forms (attenuated) of pathogenic microbes were used as vaccines. Although the attenuated microbes induce effective immune response, a significant risk of reversion to pathogenic forms remains. While in the twenty-first century, with the advent of genetic engineering, microbes can be tailored with desired properties. In this review, I have focused on the use of genetically modified bacteria for the delivery of vaccine antigens. More specifically, the live-attenuated bacteria, derived from pathogenic bacteria, possess many features that make them highly suitable vectors for the delivery of vaccine antigens. Bacteria can theoretically express any heterologous gene or can deliver mammalian expression vectors harboring vaccine antigens (DNA vaccines). These properties of live-attenuated microbes are being harnessed to make vaccines against several infectious and noninfectious diseases. In this regard, I have described the desired features of live-attenuated bacterial vectors and the mechanisms of immune responses manifested by live-attenuated bacterial vectors. Interestingly anaerobic bacteria are naturally attracted to tumors, which make them suitable vehicles to deliver tumor-associated antigens thus I have discussed important studies investigating the role of bacterial vectors in immunotherapy. Finally, I have provided important discussion on novel approaches for improvement and tailoring of live-attenuated bacterial vectors for the generation of desired immune responses.


docid: dlyzyjmw

title: Communication III (Immunological Control)

text: One of controlling systems in the body which the body also uses for communication (externally and internally) is the Immune system, based upon existence of MHC molecules fundamental for recognition, and other molecules responsible for antigen-presentation and immediate or postponed reaction to it. The fundamental unique feature of immune system cells is the capability of distinguishing “self” from “non-self” cells and proteins. Communication between different cell types of the immune system is critical in the recognition of self, surveillance, defense, and clearance of foreign invaders. These signaling mechanisms involve direct cell–cell signaling as well as autocrine and paracrine signaling. The essential feature of particular cells of immunological system is memory and although still known at the level of phenomenology, presents the basis for vaccines.


title: Genus Parapoxvirus

text: Highly contagious pustular skin infections of sheep, goats and cattle that were unwittingly transmitted to humans from close contact with infected animals, have been the scourge of shepherds, herdsmen and dairy farmers for centuries. In more recent times we recognise that these proliferative pustular lesions are likely to be caused by a group of zoonotic viruses that are classified as parapoxviruses. In addition to infecting the above ungulates, parapoxviruses have more recently been isolated from seals, camels, red deer and reindeer and most have been shown to infect man. The parapoxviruses have one of the smallest genomes of the poxvirus family (140 kb) yet share over 70% of their genes with the most virulent members. Like other poxviruses, the central core of the genomes encode factors for virus transcription and replication, and structural proteins, whereas the terminal regions encode accessory factors that give the parapoxvirus group many of its unique features. Several genes of parapoxviruses are unique to this genus and encode factors that target inflammation, the innate immune responses and the development of acquired immunity. These factors include a homologue of mammalian interleukin (IL)-10, a chemokine binding protein and a granulocyte-macrophage colony stimulating factor /IL-2 binding protein. The ability of this group to reinfect their hosts, even though a cell-mediated memory response is induced during primary infection, may be related to their epitheliotropic niche and the immunomodulators they produce. In this highly localised environment, the secreted immunomodulators only interfere with the local immune response and thus do not compromise the host’s immune system. The discovery of a vascular endothelial growth factor-like gene may explain the highly vascular nature of parapoxvirus lesions. There are many genes of parapoxviruses which do not encode polypeptides with significant matches with protein sequences in public databases, separating this genus from most other mammalian poxviruses. These genes appear to be involved in inhibiting apoptosis, manipulating cell cycle progression and degradation of cellular proteins that may be involved in the stress response, thus allowing the virus to subvert intracellular antiviral mechanisms and enhance the availability of cellular molecules required for replication. Parapoxviruses in common with Molluscum contagiosum virus lack a number of genes that are highly conserved in other poxviruses, including factors for nucleotide metabolism, serine protease inhibitors and kelch-like proteins. It is apparent that parapoxviruses have evolved a unique repertoire of genes that have allowed adaptation to the highly specialised environment of the epidermis.


title: B-Cell Targeted Therapies in Autoimmune Cytopenias and Thrombosis

text: Ever since the advent of Rituximab and subsequently the emergence of other compounds targeting B cells, a cornucopia of medical applications have been found for this family of compounds. After their establishment as standard of care in many conditions such as rituximab in lymphoma and rheumatoid arthritis, they have been progressively found to aid in the treatment of many other conditions. This area constituted a fertile area of research in the past 12 years. Physicians have investigated the B-cell depleting agents use in cases of autoimmune hematologic cytopenias such as immune thrombocytopenia, Evans syndrome, cold and warm autoimmune hemolytic anemia, and other thrombophilic disorders such as the antiphospholipid syndrome and thrombocytopenic purpura. This chapter presents a historical perspective reviewing the various studies that have been published in this field. In addition, it offers a current assessment of the evidence regarding the use of B-cell depleting agents in the aforementioned conditions.


title: The Use of Antimicrobial Nanoparticles to Control Oral Infections

text: The potential of antimicrobial nanoparticles to control oral infections is reviewed. Such particles can be classified as having a size no greater than 100 nm and are produced using traditional or more novel techniques. Exploitation of the toxic properties of nanoparticles to bacteria, fungi and viruses, in particular metals and metal oxides, and their incorporation into polymeric materials have increased markedly over the past decade. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their biocidal, anti-adhesive and delivery capabilities, is now receiving close attention. The latest insights into the application of nanoparticles within this field, including their use in photodynamic therapy, will be discussed. Possible approaches to alter biocompatibility and desired function will also be covered.


docid: byhdrgdc

title: The Biological Fight Against Pathogenic Bacteria and Protozoa

text: The animal gastrointestinal tract is a tube with two open ends; hence, from the microbial point of view it constitutes an open system, as opposed to the circulatory system that must be a tightly closed microbial-free environment. In particular, the human intestine spans ca. 200 m(2) and represents a massive absorptive surface composed of a layer of epithelial cells as well as a paracellular barrier. The permeability of this paracellular barrier is regulated by transmembrane proteins known as claudins that play a critical role in tight junctions.


title: Tuberkulose und andere durch Luft übertragbare Infektionserkrankungen: Krankenhaushygiene zur Vermeidung und Eindämmung

text: Die Tuberkulose (TB) gehört weltweit zu den am häufigsten auftretenden Infektionskrankheiten und wird fast ausschließlich über die Luft (aerogen) übertragen. Nachdem in Deutschland die Lungentuberkulosefallzahlen über Jahre hinweg stagnierten, ist seit 2013 wieder ein Anstieg der Inzidenzen zu verzeichnen (RKI 2016). Als Ursache hierfür werden die aktuellen demographischen Entwicklungen (Migration und Mobilität) gesehen. Die Kenntnis der epidemiologischen Situation ist von zentraler Bedeutung, um bei Vorliegen der Verdachtsdiagnose Tuberkulose sowie der Einbeziehung einer möglichen Resistenzproblematik frühzeitig adäquate krankenhaushygienische Maßnahmen einzuleiten. Als aerogen übertragbar werden auch die Aspergillose sowie Masern, Windpocken und Herpes zoster eingestuft (CDC 2007). Die Aspergillose ist eine relativ seltene, aber häufig letal verlaufende Pilzinfektion, die überwiegend bei immunsupprimierten Patienten auftritt. Krankenhaushygienische Schutzmaßnahmen können die Risiken einer Exposition und somit das Erkrankungsrisiko minimieren. Die zentralen Maßnahmen zur Kontrolle und Prävention von aerogen übertragbaren Infektionen sind Gegenstand dieses Kapitels.


title: Nierentransplantation

text: Die Nierentransplantation ist die effektivste Behandlungsmethode der chronischen terminalen Niereninsuffizienz. Seit den 1960er Jahren entwickelte sie sich zu einer Standardtherapie. Wichtige Voraussetzungen waren die Entdeckung des HLASystems, die Entwicklung der Immunsuppressiva sowie die technische Perfektionierung des Organerhaltes außerhalb eines lebenden Körpers. Die 5- Jahres-Überlebensrate für Allotransplantate beträgt etwa 65%, diejenige von Lebendspenden 79%. Die Einrichtung von zentralen Erfassungsstellen, wie z. B. Eurotransplant (Deutschland, Benelux- Staaten, Österreich, Slowenien), ist für die Organisation des zeitgebundenen Ablaufes von großer Bedeutung. Bei diesen Institutionen sind alle potentiellen Nierenempfänger registriert. Dort werden auch alle potentiellen Spenderorgane gemeldet und dem passenden Empfänger zugeordnet.


title: Nanomolecular Diagnostics

text: Clinical application of molecular technologies to elucidate, diagnose, and monitor human diseases is referred to as molecular diagnosis. It is a broader term than DNA (deoxyribonucleic acid) diagnostics and refers to the use of technologies that use DNA, RNA (ribonucleic acid), genes, or proteins as bases for diagnostic tests. The scope of the subject is much wider and includes in vivo imaging and diagnosis at the single-molecule level. A more detailed description of molecular diagnostics is presented elsewhere (Jain 2012a).


title: Modeling and Predicting Human Infectious Diseases

text: The spreading of infectious diseases has dramatically shaped our history and society. The quest to understand and prevent their spreading dates more than two centuries. Over the years, advances in Medicine, Biology, Mathematics, Physics, Network Science, Computer Science, and Technology in general contributed to the development of modern epidemiology. In this chapter, we present a summary of different mathematical and computational approaches aimed at describing, modeling, and forecasting the diffusion of viruses. We start from the basic concepts and models in an unstructured population and gradually increase the realism by adding the effects of realistic contact structures within a population as well as the effects of human mobility coupling different subpopulations. Building on these concepts we present two realistic data-driven epidemiological models able to forecast the spreading of infectious diseases at different geographical granularities. We conclude by introducing some recent developments in diseases modeling rooted in the big-data revolution.


title: Diagnostic Approach to Life-Threatening Pulmonary Infiltrates

text: Diagnosis of pulmonary disease is typically based upon consideration of presenting symptoms, physical examination, and pulmonary function testing in combination with classification of radiographic features, to guide diagnostic tests and initiate empiric treatment. When diagnostic efforts and/or empiric treatment fails, thoracic surgeons have traditionally been called upon to perform surgical biopsy of the lung to aid in the diagnosis of indeterminate, life-threatening pulmonary disease. Such biopsy has been requested specifically in the case of diffuse lung disease among patients receiving treatment for solid-organ or hematologic cancers, particularly when symptoms of respiratory failure progress and when noninvasive diagnostic tests and empiric treatments fail to halt progression. In such circumstances, radiologists, pulmonologists, and thoracic surgeons may be consulted and asked to provide tissue specimens that will allow rapid, accurate diagnosis leading to specific treatment. It is imperative that biopsy take place before respiratory failure supervenes [1], and that the specimens provided to clinical laboratories, pathologists, and microbiologists are comprehensive and properly preserved.


title: Pederin, Psymberin and the Structurally Related Mycalamides: Synthetic Aspects and Biological Activities

text: Pederin, psymberin, and mycalamides are related members of a relatively new family of potent natural antiviral and antitumor compounds originally isolated from marine sponges in 1988. This natural family of chemicals is of great interest to medicinal chemists and biologists, stemming from its extremely low abundance in source organisms and strikingly potent biological activity. They have clearly emerged as promising new synthetic targets, and are the focus of quite an interdisciplinary approach to molecular characterization. In this chapter we review diverse synthetic approaches to this family of natural products that has been demonstrating remarkable biological activity. We discuss relevant history, biological origins with the latest information on source organisms and their hosts, in-depth synthetic approaches, and biological data supporting their potential as therapeutic compounds.