title: Utilization Management in a Large Community Hospital

text: The utilization management of laboratory tests in a large community hospital is similar to academic and smaller community hospitals. There are numerous factors that influence laboratory utilization. Outside influences like hospitals buying physician practices, increasing numbers of hospitalists, and hospital consolidation will influence the number and complexity of the test menu that will need to be monitored for over and/or under utilization in the central laboratory and reference laboratory. CLIA’88 outlines the four test categories including point-of-care testing (waived) and provider-performed microscopy that need laboratory test utilization management. Incremental cost analysis is the most efficient method for evaluating utilization reduction cost savings. Economies of scale define reduced unit cost per test as test volume increases. Outreach programs in large community hospitals provide additional laboratory tests from non-patients in physician offices, nursing homes, and other hospitals. Disruptive innovations are changing the present paradigms in clinical diagnostics, like wearable sensors, MALDI-TOF, multiplex infectious disease panels, cell-free DNA, and others. Obsolete tests need to be universally defined and accepted by manufacturers, physicians, laboratories, and hospitals, to eliminate access to their reagents and testing platforms.


title: Public Health Informatics and the Health Information Infrastructure

text: What are the three core functions of public health, and how do they help shape the different foci of public health and medicine? What are the current and potential effects of a) the genomics revolution; and b) 9/11 on public health informatics? What were the political, organizational, epidemiological, and technical issues that influenced the development of immunization registries? How do registries promote public health, and how can this model be expanded to other domains (be specific about those domains) ? How might it fail in others?Why? What is the vision and purpose of the National Health Information Infrastructure? What kinds of impacts will it have, and in what time periods? Why don’t we have one already? What are the political and technical barriers to its implementation? What are the characteristics of any evaluation process that would be used to judge demonstration projects?


title: Discovery of Beclabuvir: A Potent Allosteric Inhibitor of the Hepatitis C Virus Polymerase

text: The discovery of beclabuvir occurred through an iterative series of structure-activity relationship studies directed at the optimization of a novel class of indolobenzazepines. Within this research, a strategic decision to abandon a highly potent but physiochemically problematic series in favor of one of lower molecular weight and potency was key in the realization of the program’s objectives. Subsequent cycles of analog design incorporating progressive conformational constraints successfully addressed off-target liabilities and identified compounds with improved physiochemical profiles. Ultimately, a class of alkyl-bridged piperazine carboxamides was found to be of particular interest, and from this series, beclabuvir was identified as having superior antiviral, safety, and pharmacokinetic properties. The clinical evaluation of beclabuvir in combination with both the NS5A replication complex inhibitor daclatasvir and the NS3 protease inhibitor asunaprevir in a single, fixed-dose formulation (Ximency) resulted in the approval by the Japanese Pharmaceutical and Food Safety Bureau for its use in the treatment of patients infected with genotype 1 HCV.


title: Transgenerational Consequences of Human Visitation

text: Human interactions with wild animals may result in changes in behavior across generations with consequences for population trends and hence threat status. Exposure to humans and tameness of animals when exposed to humans may also imply significant costs such as the rapid spread of viruses and other microorganisms that constitute reservoirs or vectors of serious diseases. Ecotourism and nature-based tourism are factors that may affect the behavior of animals living in natural habitats, including their stress and fear responses. Here I review a scarce and scattered literature dealing with changes in animal behavior across generations and critically assess the relative importance of the mechanisms that potentially underlie these changes. Animals may show short-term changes in behavior across generations as a consequence of microevolution (a genetic change in behavior), nongenetic so-called epigenetic changes, reductions in the response to behavioral stimuli with repeated exposure to a stimulus (habituation), and the nonrandom distribution of animals that differ in behavior among sites (so-called phenotypic sorting). I conclude with a plea for future research to allow assessment of the underlying causes of long-term changes in behavior of animals exposed to human disturbance, particularly those changes caused by ecotourists’ activities.


title: Late Noninfectious Pulmonary Complications in Hematopoietic Stem Cell Transplantation

text: Hematopoietic stem cell transplantation (HSCT) is an established therapeutic modality for a number of malignant and nonmalignant conditions. Pulmonary complications following HSCT are associated with increased mortality and morbidity. These complications may be classified into infectious versus noninfectious, and early versus late based on the time of occurrence post-transplant. Thus, exclusion of infectious etiologies is the first step in the diagnoses of pulmonary complications. Late onset noninfectious pulmonary complications typically occur 3 months post-transplant. Bronchiolitis obliterans is the major contributor to late-onset pulmonary complications, and its clinical presentation, pathogenesis, and current therapeutic approaches are discussed. Idiopathic pneumonia syndrome is another important complication which usually occurs early, although its onset may be delayed. Organizing pneumonia is important to recognize due to its responsiveness to corticosteroids. Other late onset noninfectious pulmonary complications discussed here include pulmonary venoocclusive disease, pulmonary cytolytic thrombi, pleuroparenchymal fibroelastosis, thoracic air leak syndrome, and posttransplant lymphoproliferative disorders.


title: Biochip Platforms for DNA Diagnostics

text: This chapter looks at the use of microlithographically fabricated biochip platforms for DNA diagnostics and prognostics, although protein and RNA biochips are also briefly considered. Biodetection methods such as ion-selective electrodes (ISEs), microelectromechanical systems (MEMS) devices such as microcantilevers, optical, piezoelectric-based acoustic wave, and mass spectrometry are briefly discussed. Emphasis is given to label-free electrochemical (impedimetric, voltammet-ric, and amperometric) detection. The production of DNA biochips is highlighted as are the operation and design of the experiments to reveal gene expression and SNP data. Applications discussed include the monitoring of microbes, cancer classification studies, and patient stratification in drug development. Finally, challenges and issues facing the development of diagnostic and prognostic biochips are discussed in detail.


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 (Pipkin D, Information security: protecting the global enterprise. Prentice Hall PTR, Upper Saddle River, 2000).


title: Leber und Gallenwege

text: Patienten mit einer akuten Gallenblasenkolik müssen im Verlauf mit erneuten Beschwerden oder Komplikationen rechnen (siehe Übersicht). Sie sollten daher so bald wie möglich einer Cholezystektomie zugeführt werden, weil sich dadurch die Morbidität während der Wartezeit für eine elektive Cholezystektomie und wiederholte notfallmäßige Vorstellungen in der Notaufnahme vermeiden lassen. Die frühe laparoskopische Cholezystektomie scheint dabei mit einer niedrigeren Konversionsrate, einer kürzeren Operationszeit und einem kürzeren Krankenhausaufenthalt einherzugehen (Duncan u. Riall 2013).


title: Reiseimpfungen und allgemein empfohlene Impfungen

text: Nach Schätzungen der World Tourism Organisation (WTO) verreisen jedes Jahr ca. 7,2 Millionen Deutsche nach Übersee. Hiervon entfällt ein Großteil auf Reisen in nicht tropische Gebiete: die USA, gefolgt von der Türkei und Tunesien, sind die häufigsten Ziele von Interkontinentalreisenden (www.world-tourism.org). Im Gegensatz hierzu sind Ost- und vor allem Westafrika, die von erkrankten Tropenrückkehrern am häufigsten als Infektionsgebiete genannt werden, bei den Reisezielen nur zu einem sehr geringen Ausmaß vertreten. Die internationale Reisetätigkeit boomt weltweit und gerade in Deutschland genießen Auslandsreisen einen besonderen Stellenwert. Die Forschungsgruppe Urlaub und Reisen gibt die Gesamtzahl der grenzüberschreitenden Reisen, die von Deutschen getätigt wurden, mit 56–63 Millionen pro Jahr an. Von den geschätzten 7,2 bis 7,8 Millionen interkontinentalen Reisen führten ca.4 Millionen in die Tropen.


title: Hygiene in der Repatriierungsmedizin

text: Nicht zu vernachlässigen sind die hygienischen Bedürfnisse des Patienten unmittelbar vor und während des Transportes.


title: Biophysik

text: In den vorhergehenden Kapiteln sind wir einmal durch unser gesamtes Weltall gewandert. Als viel aufregender und gestaltenreicher empfinden wir hingegen die biologischen Wunder, die sich täglich um uns herum auf unserem Heimatplaneten zutragen, die wir Menschen nunmehr seit etwa einer Million Jahren bewusst erleben und noch immer nicht (voll) durchschauen, obwohl auch sie den Gesetzen der Physik in Strenge zu gehorchen scheinen. Hier spielen sich alle Prozesse, wo gewünscht, direkt vor unseren Augen, Ohren, Nasen und Gefühlen ab, wir haben gelernt – nach einer Million Jahren – wo in unseren Körpern unsere Baupläne (DNS) liegen und mit welchen physikalisch-chemischen Werkzeugen (Proteinen) ihre Anweisungen ausgeführt werden, oft von Hunderten oder sogar Tausenden unterschiedlicher Makro-Moleküle zugleich, in korrelierten Aktionen. Aber bei jedem konkreten Problem enden unsere Forschungen leicht mit mehr Fragen als Antworten, mit mehr Staunen als Einsichten.


title: Health Security and Disease Detection in the European Union

text: In a globalised world, national and international institutions in charge of health security can no longer only rely on traditional disease reporting mechanisms, not designed to recognise emergence of new hazards. New approaches are developing to improve the capacity of surveillance systems in detecting previously unknown threats. More recently, surveillance institutions have been actively searching for information about health threats using internet scanning tools, email distribution lists or networks that complement the early warning function of routine surveillance systems. Since its foundation, ECDC has developed an epidemic intelligence framework that encompasses all activities related to early identification of potential health hazards, their verification, assessment and investigation, in order to recommend public health control measures. Since June 2005, about 900 threats have been monitored by ECDC. Several threats made it necessary to develop formal risk assessments or to dispatch ECDC experts to outbreak areas. Examples of recent events, identified through the epidemic intelligence activity, are presented to illustrate the course of action from threat detection through risk management in Europe.


title: Design of Real-time Systems for QoS

text: It was discovered early, that in order to achieve the desired QoS properties a design methodology for real-time systems has to include appropriate measures to ensure that the QoS criteria are considered during the entire life-cycle. These have been joined in the framework of the ISO/IEC 13236 [31] and ISO/IEC TR 13243 [32] standards for QoS in information technology, and the standard IEC 61508 [28], which includes the necessary activities for safety-related systems from a project’s start until the end of its life-cycle. Like safety, security is also an issue that is gaining importance for embedded (real-time) applications [76], and which must be dealt with during the design phase, too.


title: Global Emerging Pathogens, Poverty and Vulnerability: An Ethical Analysis

text: In the last few decades, the world has witnessed the emergence and re-emergence of new and old infectious diseases. Emerging infectious diseases (EIDs) have the capacity to spread rapidly from one region of the world to another, within a very short time, due to world travel and increased global interdependence. The impact of this varies from one region to another. Resource poor countries suffer the most due to an already high disease burden, poor infrastructures, lack of clean, potable water and sanitation, as well as an acute shortage of qualified health personnel to manage, control and contain the crisis/spread. Poor and marginalized communities are the most vulnerable because infectious diseases cause not only suffering and death, but also severe economic hardship. The outbreak of HIV/AIDS, tuberculosis and Ebola Virus Disease (EVD) in the developing world has shown the extent to which economic and social conditions can affect vulnerable populations. These socio-economic, cultural and environmental conditions accelerate the spread of, and exacerbate the negative impact of emerging pathogens. This chapter will undertake an analysis of the trend in global emerging pathogens, their economic impact, the global vulnerability status and ethical implications.


title: Biocontainment Principles for Pediatric Patients

text: The need for medical communities to prepare for highly hazardous communicable disease outbreaks was perhaps best exemplified in the 2014–2016 Ebola virus outbreak. To date, most efforts of preparedness have focused on adult medical providers, though it is critical that pediatric institutions achieve the same level of preparedness for children who may present with these illnesses. Care of pediatric patients exposed and/or infected with these unique pathogens requires advanced planning and training in order to offer the highest level of care while at the same time being able to ensure the safety of both the hospital staff and the community. In this chapter, we will discuss the basic principles of biocontainment and care in a unique pediatric setting and offer guidelines on how to navigate the identification, isolation, family-centered care, and clinical care of children with highly hazardous communicable diseases.


title: Parvovirus

text: Name of Virus: Parvovirus


Legal problems of pharming


title: Laboratory Methods for Detecting Viral Infections

text: The first methods for detection of bacterial infections were available around 1880. After staining, bacterial pathogens were recognized in the light microscope because of their size and could be cultivated in culture media. Viruses evaded this approach, as they are significantly smaller, and as obligate parasites are not able to multiply in cell culture media. Although some viral infections could be associated with specific cellular changes and certain depositions in the infected tissue around the turn of the century, e.g. Negri inclusion bodies in nerve cells during rabies, a specific diagnosis was only possible through the development of cell culture methods and modern molecular biology. Today, viral infections can be detected directly by determining the agents, individual viral proteins, or their genetic information, or other materials in the blood of infected people or animals by using appropriate methods. Direct detection of viruses is possible, with the exception of latent or persistent infection forms, only during the acute phase of the disease. In some cases, the pathogens are present in the infected organism only before the symptomatic phase, so the direct detection of the virus is frequently not successful. Therefore, infections or contact with pathogens is usually demonstrated in virus diagnostics indirectly by characterization of the developing specific immune response.


title: Human Security in East Asia: Assembling a Puzzle

text: This chapter describes the motivation of the research project, provides the theoretical framework of the entire book, and gives a summary of the findings of the case study chapters. In the process of diffusion of human security norms in East Asia, several features have emerged. First, East Asians have accepted a comprehensive definition of human security regarding the perception of threats. Second, East Asians tend to think that human security and state security are complementary. Third, the constituent elements of the human security norms such as freedom from fear and from want, freedom to live in dignity, protection, and empowerment are already accepted by East Asian nations. We need an extra effort to elevate human security to a full-fledged norm in the region.


title: Pediatric Natural Deaths

text: Autopsies are important in the investigation of childhood deaths. Most natural deaths are unlikely to come to the attention of the forensic pathologist, particularly in cases where death occurs in hospital. During the neonatal period (up to 28 days of age), deaths most commonly occur as a result of prematurity and related conditions, chromosomal abnormalities, or congenital malformations. Beyond the neonatal period, trauma-related deaths and sudden infant death syndrome are more common. In terms of natural acquired diseases of childhood, certain conditions are prevalent based on age and may be encountered at autopsy. Common acquired diseases that cause death in infants and children up to 5 years of age include pneumonia and other respiratory diseases, other infectious diseases, and malignancies. In older children, mortality due to natural disease declines substantially with trauma being the major cause of death, and malignancies the major cause of acquired disease. Sudden and/or unexpected deaths in which a natural disease state was previously unknown are most likely to come under the jurisdiction of the medical examiner or coroner and may be related to an underlying natural disease. Depending on the underlying disease process, the approach can differ, and therefore familiarity with common causes of death during childhood is important in order to focus the autopsy so that special techniques can be used along with obtaining proper ancillary testing to arrive at an accurate diagnosis and cause of death.


title: Herpetofauna Used in Traditional Folk Medicine: Conservation Implications

text: This chapter provides an overview of the global use of herpetofauna in traditional folk medicine and the implications for conservation. The results indicate that 331 species (284 reptiles and 47 amphibians) are used in traditional folk medicine around the world. Among the species recorded, 182 reptiles and 42 amphibians are listed in the IUCN Red List. Additionally, 93 reptiles are in some of the appendices of CITES. These numbers demonstrate the importance of understanding such medicinal uses in the context of reptile conservation as well as the need for considering sociocultural factors when establishing management plans directed toward the sustainable use of these reptiles.


title: Differential Diagnosis of Asthma

text: Asthma is one of the most common chronic syndromes worldwide (Moorman et al., Vital Health Stat 3(35), 2012). It is not a diagnosis but a clinical syndrome based on a constellation of signs and symptoms (Li et al., Ann Allergy Asthma Immunol 81:415–420(IIa), 1998). The classic symptoms of asthma include chest tightness, wheeze, cough, and dyspnea (Moorman et al., Vital Health Stat 3(35), 2012). The term asthma encompasses a spectrum of pulmonary diseases sharing the hallmark of reversible airway obstruction and can be classified as allergic or non-allergic (Löwhagen, J Asthma. 52(6):538–44, 2015). Asthma designated allergic is due to an immunoglobulin E (IgE)-mediated process, but as noted not all asthma is allergic in etiology (Romanet-Manent et al., Allergy 57:607–13, 2002). The differential diagnosis for asthma is broad and requires a detailed history with supportive pulmonary function tests to be properly diagnosed.


title: Pathogenesis of Sepsis

text: Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Both hyperinflammation and immune suppression ensue, to an extent that is harmful to the host. The inflammatory balance is disturbed, and this is associated with a failure to return to homeostasis. All pathogens with sufficient load and virulence can cause sepsis, after they succeed to adhere and pass the mucosal barrier of the host. The host defense system can recognize molecular components of invading pathogens, called pathogen-associated molecular patterns (PAMPs), with specialized receptors known as pattern recognition receptors (PRRs). Through several signaling pathways, overstimulation of PRRs has proinflammatory and immune suppressive consequences. Hyperinflammation is characterized by activation of target genes coding for proinflammatory cytokines (leukocyte activation), inefficient use of the complement system, activation of the coagulation system, and concurrent downregulation of anticoagulant mechanisms and necrotic cell death. The release of endogenous molecules by injured cells, called danger-associated molecular patterns (DAMPs) or alarmins, leads to deterioration in a vicious cycle by further stimulation of PRRs. Features of immune suppression are massive apoptosis and thereby depletion of immune cells, reprogramming of monocytes and macrophages to a state of a decreased capacity to release proinflammatory cytokines and a disturbed balance in cellular metabolic processes.


title: Plant Endogenous Retroviruses? A Case of Mysterious ORFs

text: Endogenous retroviruses have traditionally been defined as descendants of extinct retroviruses that infected and integrated into the chromosomes of host germ-line cells and were thereafter transmitted vertically as part of host genomes. Most retain at least the vestiges of genes once required for infectious horizontal transfer, namely envelope genes. In contrast, the long evolutionary histories of retrotransposons are presumed not to have included infectious ancestors. With the characterization of the Gypsy retrotransposon in Drosophila melanogaster as an infectious, endogenous retrovirus, these distinctions have blurred. A number of plant LTR retroelements possess coding regions whose conceptual translations produce hypothetical proteins with predicted structural elements found in viral envelope proteins, and the term endogenous retrovirus began to be applied to these elements. The question of whether any of the many plant retroelement genes now annotated as “env-like” generate proteins that have or had envelope functions remains unanswered. This review reevaluates the available data.


title: Employing Live Microbes for Vaccine Delivery

text: The employment of live attenuated vaccines has a long-standing record in human and veterinary medicine. Most of the vaccines in current use were empirically developed during the last century. Today, due to the great advances in fields such as immunology and bioengineering, the rational development of live attenuated vaccines becomes increasingly feasible. Moreover, live vaccines can be used as carrier systems for heterologous antigens or therapeutic factors. In each case, the development of a recombinant live attenuated vaccine is a complex task where properties such as targeting specificity, antigen synthesis, antigen release, and safety aspects have to be integrated. A range of such recombinant vaccine candidates have successfully been tested in the clinics, but very few have been approved so far. In many cases, further optimization of such vaccines is necessary with regard to their efficacy and safety profiles. In the present chapter, we focus on current strategies which are employed for the development of new and the optimization of first generation recombinant live vaccines based on bacteria and viruses.


title: East Asian Regionalism: The Macroregional Dimensions of Relations

text: This chapter presents macroregional dimension of East Asian regionalism. In this context, two structures that are the base of relations in the region are described: APT and EAS.


title: Foundations for the Study of Structure and Function of Proteins

text: Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells. Moreover, proteins exhibit enormous diversity of biological function and are the most final products of the information pathways. Protein is a major component of protoplasm, which is the basis of life. It is translated from RNA and composed of amino acid connected by peptide bonds. It participates in a series of complicated chemical reactions and finally leads to the phenomena of life. So we can say it is the workhorse molecule and a major player of life activity. Biologists focus on the diction of structure and function of proteins by the study of the primary, secondary, tertiary, and quaternary dimensional structures of proteins, posttranscriptional modifications, protein-protein interactions, the DNA-proteins interactions, and so on.


title: Consultative and Comanagement

text: This chapter covers the role of the hospitalist as a consultant and their interaction with surgical specialties. Included are discussions of perioperative care in the hospital and clinic. Oral and parenteral nutrition for the hospitalized patient are examined. A special emphasis is placed on palliative care for the hospitalized patient. Comanagement of surgical patients with an emphasis on orthopedics is reviewed.


title: The Emerging Threat of Ebola

text: Ebola is one of the deadliest infectious disease of the modern era. Over 50% of those infected die. Prior to 1976, the disease was unknown. No one knows exactly where it came from, but it is postulated that a mutation in an animal virus allowed it to jump species and infect humans. In 1976 simultaneous outbreaks of Ebola occurred in what is now South Sudan and the Democratic Republic of the Congo (DRC). For 20 years, only sporadic cases were seen, but in 1995 a new outbreak occurred killing hundreds in the DRC. Since that time the frequency of these outbreaks has been increasing. It is uncertain why this is occurring, but many associate it with increasing human encroachment into forested areas bringing people and animals into more intimate contact and increased mobility of previously remote population. This chapter will navigate Ebola in the context of global health and security. There are multiple objectives of this chapter. First is to provide a basic understanding of Ebola disease processes and outbreak patterns. Second, is to explore the interplay between social determinants of health and Ebola. The role of technology in spreading Ebola outbreaks will be explained as will Ebola’s potential as a bioweapon. Readers will gain understanding of the link between environmental degradation and Ebola outbreaks. This chapter will be divided into five main sections. These are (1) a case study; (2) Ebola Disease process; (3) Social determinants of health and Ebola; (4) Ebola in the modern era, and (5) the link between Ebola and environmental degradation.


title: Grundlagen der systemischen Therapie

text: Die Einführung sog. »zielgerichteter Medikamente« hat einen Paradigmenwechsel in der Systemtherapic maligner Erkrankungen ausgelöst. Voraussetzung hierfür waren die in den letzten 25 Jahren gesammelten Erkenntnisse der molekularbiologischen, molekulargenetischen und immunologischen Grundlagenforschung, die ein besseres Verständnis der pathogenetischen Prozesse im Rahmen der malignen Transformation und Tumorprogression sowie die Identifikation strategischer Zielstrukturen (»Targets«) ermöglichen. Auf diese Weise wurde ein neuer Ansatz der Entwicklung antineoplastischer Therapeutika angestoßen, der auf die Wirkung an spezifischen Molekülaktivitäten und nicht primär auf zelluläre Endpunkte (Wachstumshemmung, Zelltod) ausgerichtet ist.


title: Epidemiology

text: The term “epidemiology” was originally used for the science of major, humanity-threatening diseases. Today, it refers to the science of all transmissible and non-transmissible diseases in a population, irrespective of whether they occur frequently in time or space. In the field of microbiology, epidemiology deals with diseases which are caused by transmissible agents such as bacteria, viruses or prions, and in particular with the spread and consequences of infections. Therefore, epidemiological studies are very important for the health of the world population, and are the basis for general and veterinary measures such as quarantine or vaccinations to prevent and control pandemics and epidemics. Furthermore, they allow the development of guidelines and regulations for vaccinations and other measures that prevent infections.


title: Antivirals for the common cold

text: Despite a 60-year history of discovery, trial and evaluation of scores of different compounds, there are no currently licensed effective antivirals for the common cold. The history of the development and abandonment of all potential compounds so far teaches us some important lessons for the continuation of our fight against colds. First, the common cold is a benign self-limiting condition, making the consumption of ‘harmless’ antivirals a requisite of prime importance for regulators. Second, the common cold is a syndrome caused by a myriad of known and unknown agents, which reduces the effectiveness of compounds that interfere with single specific agents or types of agents. The multifactorial nature of the genesis of colds makes it difficult for compounds showing in vitro efficacy to ‘make the jump’ to field effectiveness. Last, despite the heavy burden that the cold imposes on society, the vagueness and shortness of symptoms make it difficult for sufferers to present in time for physicians to prescribe antivirals, which are only effective if taken within a short time frame. Attention should be paid to the development of compounds with a non-virus-specific action.


title: Infektiologie

text: Die Infektiologie ist ein Gebiet, das zahlreiche Schwerpunkte der Inneren Medizin, wie z. B. die Pulmologie oder Gastroenterologie, streift. Entsprechend behandelt das Kapitel alle wichtigen und häufigen Infektionen, mit denen ein Internist in der Praxis konfrontiert sein kann: von den unterschiedlichen Pneumonieformen, der Tuberkulose und Influenza über Noro-Virus-Erkrankungen, Cholera und EHEC-Infektionen bis hin zu sexuell übertragbaren Erkrankungen (HIV, Lues, Gonorrhö), die unterschiedlichen Herpes-Virus-Infektionen (Varizella-Zoster-, Herpes-simplex-, Eppstein-Barr- und Zytomegalie-Virus-Infektionen), Mykosen (Candidiasis, Aspergillose etc.) und andere häufig vorkommende Infektionskrankheiten.


Regulatory Aspects in Using Surrogate Markers in Clinical Trials


title: Continuities and Change in IPE at the Start of the Twenty-first Century

text: This chapter reviews changes and continuities for the development of International Political Economy (IPE) in the twenty-first century. We highlight four themes, which authors in this handbook subsequently explore. These include necessary adaptations of IPE theory in response to changing global conditions; how global reordering affects global economic governance, production, and power relations; the diverse global crises to which actors must respond, often under intense time pressure; and a variety of emerging IPE issues on which we need new and/or more attention from IPE scholars and students. We conclude by identifying five trends which we argue would help enhance IPE understandings, ensure the policy relevance of our discipline, and prepare our students in the coming decade.


title: DNA helicase 3.6.4.12

text: EC number 3.6.4.12 Systematic name ATP phosphohydrolase (DNA helix unwinding) Recommended name DNA helicase Synonyms 3’ to 5’ DNA helicase <28> [35] 3’-5’ DNA helicase <11> [55] 3’-5’ PfDH <11> [55] 5’ to 3’ DNA helicase <26,27> [19,42] AvDH1 <47> [37] BACH1 helicase <19> [34] BLM <3> [28] BLM protein <3> [28] BRCA1-associated C-terminal helicase <19> [34] BcMCM <8> [52] CeWRN-1 <43> [9] DDX25 <3,48> [36] DNA helicase 120 <7> [15] DNA helicase A <4> [8] DNA helicase E <5> [44] DNA helicase II <9> [7] DNA helicase III <4> [27] DNA helicase RECQL5β <44> [17] DNA helicase VI <3> [45] Dbp9p <46> (<46> a member of the DEAD box protein family [24]) [24] DmRECQ5 <1> [50] DnaB helicase <29> [23] E1 helicase <17> [58] GRTH/DDX25 <3,48> [36] HCoV SF1 helicase <23> [3] HCoV helicase <23> [3] HDH IV <3> [45] Hel E <5> [44] Hmi1p <40> [60] MCM helicase <6,5,38> [43,54] MCM protein <6,35> [43] MER3 helicase <22> [30] MER3 protein <22> [30] MPH1 <28> [35] NS3 <12,50> (<12,50> ambiguous [38,65,66]) [38,65,66] NS3 NTPase/helicase <14> (<14> ambiguous [67]) [67] NS3 protein <12> (<12> ambiguous [63]) [63] NTPase/helicase <12,16> (<12> ambiguous [61]) [61,64] PDH120 <7> [15] PIF1 <33> [51] PIF1 helicase <33> [51,53] PcrA <37> [20] PcrA helicase <37,41,49> [20,21,39] PcrASpn <41> [21] PfDH A <11> [55] Pfh1p <27> [42] RECQ5 <1> [49,50] RECQ5 helicase <1> (<1> small isoform [49]) [49] RECQL5b <44> [17] REcQ <31> [13] RSF1010 RepA <30> [5] RecG <45> [6] RecQ helicase <32> [56] RecQsim <32> [56] Rep52 <24> [40] Rrm3p <26> [19] Sgs1 <36> [29] Sgs1 DNA helicase <36> [29] TWINKLE <21> [33] Tth UvrD <20> [16] UvrD <20,42> [16,22] UvrD helicase <39> [18] WRN <18> [31] WRN RecQ helicase <18> [12] WRN helicase <18> [12] WRN protein <18> [12] WRN-1 RecQ helicase <43> [9] Werner Syndrome helicase <18> [31] Werner syndrome RecQ helicase <18> [12] dheI I <1> [46] dnaB <29> [23] hPif1 <33> [53] helicase DnaB <2> [10] helicase II <25> [25] helicase PcrA <49> [39] helicase UvrD <20> [16] helicase domain of bacteriophage T7 gene 4 protein <10> [47] non structural protein 3 <12> (<12> ambiguous [61,62]) [61,62] nonstructural protein 3 <12,14,50,51> (<12,14,50> ambiguous [38,63,65,66,67]; <51> ambigous [4]) [4,38,63,65,66,67] protein NS3 <12> (<12> ambiguous [62]) [62] scHelI <4> [26] urvD <25> [25]


title: The History of Fluid Resuscitation for Bleeding

text: Damage control resuscitation (DCR) is a bundle of care first described by Holcomb et al. that is aimed at reducing death from hemorrhage for patients with severe traumatic bleeding. DCR principles include compressible hemorrhage control; hypotensive resuscitation; rapid surgical control of bleeding; avoidance of the overuse of crystalloids and colloids, prevention or correction of acidosis, hypothermia, and hypocalcaemia; and hemostatic resuscitation (blood-based resuscitation). Remote damage control resuscitation (RDCR) is defined as the prehospital application of DCR concepts. The term RDCR was first published by Gerhardt and has been disseminated by the (Trauma Hemostasis and Oxygenation Research), or THOR Network. The history of DCR and RDCR starts well before the inception of the terms. The concepts behind the principles of DCR and RDCR stretch far back into the past. This chapter provides an outline of this history, but it is limited to the fluid resuscitation aspect of DCR/RDCR.


Avida: Evolution Experiments with Self-Replicating Computer Programs


title: Infectious Diseases and Microbiological Threats

text: “The time to close the book on infectious disease” is far from near. Infections seem to be here to stay and have increased in importance in spite of enormous success in the field of prophylactic efforts, hygiene, vaccinology, and treatment. A large number of new agents and infections have appeared during the last decades. Conditions earlier thought to have other etiologies are today known to be distinct and have been proven to be of infectious origin. Infections alone can constitute major incidents, or they can be part of or a consequence of an incident. Even in the relatively new incident category of terrorism, infections must be seriously considered. Climate change and other changes in nature today constitute major threats of increasing infectious incidents. The increasing problem with antimicrobial resistance is, at present, considered to be one of the strongest disease threats. Infectious incidents are unique in the sense that they usually have an insidious onset, have a time span before they are detected as present or even as serious. Once the infection has started to spread, the development and increase can be extremely quick, even logarithmic. The extent of infectious incidents can be larger than that of most other disasters, and is best exemplified through different pandemics. The most important weapon to control infectious outbreaks or epidemics is active surveillance, leading to different kind of actions.


title: Networks and Models with Heterogeneous Population Structure in Epidemiology

text: Heterogeneous population structure can have a profound effect on infectious disease dynamics, and is particularly important when investigating “tactical” disease control questions. At times, the nature of the network involved in the transmission of the pathogen (bacteria, virus, macro-parasite, etc.) appears to be clear; however, the nature of the network involved is dependent on the scale (e.g. within-host, between-host, or between-population), the nature of the contact, which ranges from the highly specific (e.g. sexual acts or needle sharing at the person-to-person level) to almost completely non-specific (e.g. aerosol transmission, often over long distances as can occur with the highly infectious livestock pathogen foot-and-mouth disease virus—FMDv—at the farm-to-farm level, e.g. Schley et al. in J. R. Soc. Interface 6:455–462, 2008), and the timescale of interest (e.g. at the scale of the individual, the typical infectious period of the host). Theoretical approaches to examining the implications of particular network structures on disease transmission have provided critical insight; however, a greater challenge is the integration of network approaches with data on real population structures. In this chapter, some concepts in disease modelling will be introduced, the relevance of selected network phenomena discussed, and then results from real data and their relationship to network analyses summarised. These include examinations of the patterns of air traffic and its relation to the spread of SARS in 2003 (Colizza et al. in BMC Med., 2007; Hufnagel et al. in Proc. Natl. Acad. Sci. USA 101:15124–15129, 2004), the use of the extensively documented Great Britain livestock movements network (Green et al. in J. Theor. Biol. 239:289–297, 2008; Robinson et al. in J. R. Soc. Interface 4:669–674, 2007; Vernon and Keeling in Proc. R. Soc. Lond. B, Biol. Sci. 276:469–476, 2009) and the growing interest in combining contact structure data with phylogenetics to identify real contact patterns as they directly relate to diseases of interest (Cottam et al. in PLoS Pathogens 4:1000050, 2007; Hughes et al. in PLoS Pathogens 5:1000590, 2009).


title: Finding Those at Risk, China’s Way

text: One of the people who heard Vice Premier Wu Yi’s plea for greater openness in the aftermath of the SARS epidemic was Li Keqiang, now China’s Premier but at the time the Party Secretary of Henan province. As we saw in Chap. 10.1007/978-981-10-3746-7_2, national specialists such as Xiwen Zheng estimated the number of HIV-infected plasma sellers in Henan at around 80,000, and activists were claiming ten times as many. However, provincial officials stuck stubbornly to an estimate of 10,000 infections. Backed by the central government’s renewed determination to find out the true extent of the epidemic, Li Keqiang encouraged his staff to do whatever was necessary to get to the truth.


title: Host Immune Responses to SARS Coronavirus in Humans

text: The severe acute respiratory syndrome (SARS) is a newly identified infectious disease caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. The risk of SARS reemergence in humans remains high due to the large animal reservoirs of SARS-CoV-like coronavirus and the genome instability of RNA coronaviruses. An epidemic in 2003 affected more than 8,000 patients in 29 countries, with 10% mortality. SARS infection is transmitted by air droplets. Clinical and laboratory manifestations include fever, chills, rigor, myalgia, malaise, diarrhea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase, alanine aminotransferase, and creatine kinase activities. Health care workers are a high-risk group, and advanced age is strongly associated with disease severity. Treatment has been empirical, and there is no licensed SARS vaccine for humans so far. However, presence of long-lived neutralizing antibodies and memory T- and B-lymphocytes in convalescent SARS patients raises hope for active immunization. Furthermore, results from preclinical SARS vaccines expressing spike protein to elicit neutralizing antibodies and cellular responses that are protective in mouse and nonhuman primate models are encouraging. Very little is known of the early events in viral clearance and the onset of innate and inflammatory responses during the SARS infection. Regulation of the innate immune response is associated with the development of adaptive immunity and disease severity in SARS infection. Notably, SARS-CoV has evolved evasive strategies to suppress antiviral type I interferon responses in infected cells. In addition, inflammatory responses are characterized by upregulation of proinflammatory cytokines/chemokines such as IL-6, IP-10, and MCP-1 in tissues and serum, and massive infiltrations of inflammatory cells such as macrophages in infected tissues. Due to the lack of animal models that mimic the clinical manifestations of human SARS infection for mechanistic study and vaccine evaluation, development of a safe prophylactic SARS vaccine for human use remains a huge challenge. This chapter is written to summarize and highlight the latest clinical, serological, and immunological parameters relevant to the pathogenesis and protective immunity of SARS infection in humans.


title: Apocalypse how?

text: The probability of humankind’s long-term survival is encouragingly high, roughly 70%. This implies survival long enough to colonize the solar system and perhaps the galaxy either with Homo sapiens or some sort of conscious artificial creatures that we regard as our intellectual descendants (cyborgs, androids, whatever).


title: Hematology

text: —stress (Gaisböck’s syndrome), decreased intravascular volume


title: The Impact of Ebola Virus Disease on Government Expenditure in Sierra Leone

text: Ebola Virus Diseases (EVD) epidemic had a pronounced socio-economic impact in Guinea, Liberia and Sierra Leone, which led to a considerable negative effect on the total governments' budgets. One of the Ebola-welfare transmission mechanism is the decreasing government revenue resulting from the closure of mining and food companies of the affected countries, which impact negatively on the growth of the economy and government expenditures of the affected country. This study investigates the effect of Ebola outbreak on the capital expenditure of the Sierra Leonean government. The study employs Endogenous Growth Model of Public Expenditure, which assumes that Gross National Income (GNI) growth is determined by forces governing the production process rather than by forces outside it. The data for the study were obtained from the World Bank Data repository and the International Monetary Fund, and covered the period 2006–2014. The results show that EVD impacted negatively on government capital expenditure in Sierra Leone. Hence, it is suggested that focus should be given more to the prevention of the epidemic of communicable disease.


title: Entzündliche Erkrankungen

text: Unter einer Meningitis versteht man eine Entzündung von Pia mater und Arachnoidea. Das Erregerspektrum ist weit und reicht von Bakterien, die hämatogen-metastatisch, fortgeleitet oder durch offene Hirnverletzung zur eitrigen Meningitis führen, über Viren zu Pilzen und Parasiten. Insbesondere bei den unbehandelt häufig letal verlaufenden eitrigen Meningitiden ist eine rasche Diagnose mit Erregernachweis notwendig. Unverzüglich ist daraufhin eine spezifische, der regionalen Resistenzentwicklung angepasste Therapie einzuleiten. Die meningeale Affektion im Rahmen einer Listeriose oder Tuberkulose verdient aufgrund des klinischen Bildes, des Verlaufs und der spezifischen Therapie besondere Beachtung. Die fungalen Infektionen werden, da klinisch häufig als Meningoenzephalitis imponierend, in Abschn. 33.3 abgehandelt.


title: Case Study 3: The World Health Organization (WHO)

text: The WHO is the UN specialized agency for health and was formally established on April 7, 1948 (Lee 2009: 1-45; Burci and Vignes 2004: 15-19). Its ultimate goal is the “attainment by all peoples of the highest possible level of health” as stipulated in Article 1 of the WHO constitution. The broad definition of health as one of the fundamental human rights of all peoples and the principle of universality are key elements in the constitution of the WHO, which makes frequent reference to “all peoples”, stipulates that membership is open to “all states” and, in contrast to other UN organizations, allows membership based on a simple majority of votes in the WHA, instead of on a two-thirds majority. As of April 2012, the WHO had 193 member states and two associate members.


title: Pneumologie

text: Alter, Geschlecht, BMI (Body Mass Index). Vorerkrankungen: Hypertonie, KHK, Myokardinsuffizienz, Myokardinfarkt. Voroperationen. Fieber, Belastbarkeit, Unwohlsein. Nikotinabusus. Medikamente, Drogenkonsum. Berufliche Exposition: Gase, Dämpfe, Staub. Genetische Exposition: Familienanamnese, α1-Proteinase-Inhibitor-Mangel;


title: Public Health Laboratories

text: This chapter will review the multiple functions of Public Health Laboratories (PHLs), including their differences to commercial clinical laboratories. For example, the types of samples submitted to PHLs differ from those submitted to commercial clinical laboratories. PHLs are critically important to population based healthcare; playing an essential role in the detection of disease outbreaks. This chapter will describe the hierarchical organization of the PHL system in the Unites States, as well as the networks that have been created to support diverse PHL functions such as food safety testing and emergency response to terrorisms or natural disaster. It will briefly describe the standards used by PHLs and how the implementation of standards should further improve patient safety as a whole. In this chapter the reader will be introduced to PHL informatics in the context of the laboratories operational workflow – from test ordering, interfacing with diagnostic instruments, quality control and result reporting and analysis. The reader will also understand the impact of PHL informatics collaboration efforts and its effect on ongoing policy development.


title: Akute Gastroenteritis und postenteritisches Syndrom

text: Die akute Gastroenteritis ist im Säuglings- und Kleinkindesalter häufig. Die überwiegende Anzahl der Kinder, die an einem Brechdurchfall erkranken, ist jünger als 1 Jahr. Durch den schweren Wasser- und Elektrolytverlust kommt es zur Dehydratation. Bei 70 % der Patienten tritt eine isotone, bei 10 % eine hyponatriämische und bei 20 % eine hypertone (hypernatriämische) Dehydratation auf. Der Typ der Dehydratation ist unabhängig vom Erreger. Der Flüssigkeitsverlust kann das 2- bis 3-Fache des zirkulierenden Blutvolumens betragen, nämlich 150–250 ml/kg KG/Tag. Um das Blutvolumen konstant zu halten, entzieht der Körper dem Intrazellularraum Flüssigkeit. Dies führt zur Exsikkose. Das Ausmaß des Flüssigkeitsverlusts wird klinisch beurteilt und nach der WHO in drei Schweregrade eingeteilt (Tab. 119.1 ). Die Schleimhaut des Dünndarms setzt sich aus zwei verschiedenen Zelltypen zusammen: den reifen Enterozyten, die die Hydrolyse und Absorption von Nahrungsstoffen übernehmen – sie befinden sich in der Mitte und Spitze der Zotten – und; den unreifen Kryptenzellen, die durch Zellteilung aus Stammzellen die lebenslange Reserve für die an der Zottenspitze abgestoßenen Enterozyten darstellen. Sie sind sekretorische Zellen, die über den in den Kryptzellen lokalisierten CFTR („cystic fibrosis transmembrane conductance regulator“) Cl(–) in das Kryptenlumen sezernieren.


title: Return to Play After Infectious Disease

text: Acute illnesses are of significant concern for the health and performance of athletes. Sports medicine physicians face the challenge of promoting sufficient recovery and responding to the demands of the coaches and athletes. This chapter presents the evidence behind the risk factors for acute illness in athletes, the negative consequences of sports participation during illness and the recommendations for safe sports participation. Risk factors for infection and illness may be intrinsic (e.g. postexercise suppression of the immune system, recent acute illness, female gender) and extrinsic (e.g. training load, nutrition, resting periods). Fever during illness contributes to systemic symptoms such as headache and myalgia but also to dehydration, muscle breakdown and reduction in cardiometabolic function. The consequences of exercise during illnesses may be aggravation of illness, loss of muscle strength and endurance, cardiac complications, transmission of infection to others, neurological dysfunctions including coordination problems, rhabdomyolysis and in the worst case sudden death. Recommendations for safe return to sport include clearance of infection allowing full recovery and thereafter gradual progress of exercise volume combined with monitoring of remaining symptoms of illness. Different actions can be taken to prevent acquiring, aggravating and spreading of infections by the athlete (e.g. hygiene, physical contact, covering of the body, sharing of equipment, nutrition), the coaches (e.g. individualised plan of training, competition, nutrition, recovery and recovery measures) and the physicians (monitor and implement illness prevention, identify and arrange for high-risk athletes, educate athletes and staff).


title: Aging, Immunity, and Neuroinflammation: The Modulatory Potential of Nutrition

text: Aging influences an organism’s entire physiology, affecting functions at the molecular, cellular, and systemic levels and increasing susceptibility to many major chronic diseases. The changes in the immune system that accompany human aging are very complex and are generally referred to as immunosenescence. The factors and mechanisms of immunosenescence are multiple and include, among others, defects in the bone marrow, thymic involution, and intrinsic defects in the formation, maturation, homeostasis, and migration of peripheral lymphocytes. Aging affects both the innate and adaptive arms of the immune system. The process of aging is commonly accompanied by low-grade inflammation thought to contribute to neuroinflammation and to many age-related diseases. Numerous attempts to define the role of chronic inflammation in aging have implicated chronic oxidative stress, mitochondrial damage, immunosenescence, epigenetic modifications, and other phenomena. Several lifestyle strategies, such as intervening to provide an adequate diet and physical and mental activity, have been shown to result in improved immune and neuroprotective functions, a decrease in oxidative stress and inflammation, and a potential increase in individual longevity. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, holistic approach to determining the optimal nutritional and behavioral strategies that would maintain immune and other physiological systems in elderly people. In this chapter, we focus first on the age-related changes of the immune system. Further, we discuss possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. Finally, we consider our current understanding of the modulatory potential of nutrition that may mediate anti-inflammatory effects and thus positively affect immunity and the aging brain.


title: Computational Biosensors: Molecules, Algorithms, and Detection Platforms

text: Advanced nucleic acid-based sensor-applications require computationally intelligent biosensors that are able to concurrently perform complex detection and classification of samples within an in vitro platform. Realization of these cutting-edge computational biosensor systems necessitates innovation and integration of three key technologies: molecular probes with computational capabilities, algorithmic methods to enable in vitro computational post processing and classification, and immobilization and detection approaches that enable the realization of deployable computational biosensor platforms. We provide an overview of current technologies, including our contributions towards the development of computational biosensor systems.


title: Risks and Epidemiology of Infections After Intestinal Transplantation

text: Intestinal transplantation has become a well-accepted and successful procedure to save the lives of patients suffering from intestinal failure and who have developed life-threatening complications of parenteral nutrition. Advances in all aspects of care, from the role of multidisciplinary intestinal rehabilitation services prior to transplant to the development strategies for early recognition of infectious sequelae and even the increasing availability of preventive strategies, have led to improved outcomes and a dramatic decline in infection-associated morbidity and mortality in children undergoing intestinal transplantation. Improvements in surgical techniques and immunosuppressive regimens have been essential components in these improvements, reducing risk of infection through reduction of technical complications and more optimal immunosuppression regimens. In addition, the development of molecular tools for early recognition of viral pathogens and an understanding of the timing and risks for infection have allowed for earlier and more successful treatments. Despite these improvements, infectious sequelae remain an important problem in this population, and additional efforts are needed to further minimize the risk of infectious sequelae in those children requiring this procedure.


title: Infektionskrankheiten weltweit: Epidemiologie, Erfassung, Surveillance

text: Nach aktueller WHO-Statistik (2005) liegen Infektionskrankheiten mit 41 % der Todesfälle weltweit als häufigste Todesursache deutlich vor den Herz-Kreislauf- Erkrankungen (20 %), den Krebserkrankungen (18 %) und den zerebrovaskulären Erkrankungen (13 %). Bezogen auf die regionale Verteilung ergeben sich allerdings hierbei erhebliche Unterschiede, so dass für die Drittländer die Letalität durch Infektionskrankheiten deutlich höher als 60 % rangieren kann (► Abb. 1). Bezüglich der Häufigkeitsverteilung der Infektionskrankheiten stehen Pneumonien an erster Stelle vor Tuberkulose, Gastroenteritiden, Malaria, AIDS und Hepatitis B.


Current status of therapy of SARS


title: Respiratory Viruses in the Neonatal Intensive Care Unit

text: Respiratory viral infections (RVIs) pose a unique challenge for clinicians in the neonatal intensive care unit (NICU) due to preterm infants’ increased susceptibility to infections (Maitre NL and Williams JV, Res Rep Neonatol. 6:41–49, 2016). RVIs often present with nonspecific symptoms and currently lack effective treatments (Baraldi et al., Ital J Pediatr. 40:65, 2014). Death due to viral bronchiolitis is a major cause of morbidity and mortality in developing nations and industrialized nations alike, and patients with bronchiolitis frequently require intensive care and use of mechanical ventilation (Thompson et al., JAMA 289:179–186, 2003). Infants who acquire RVI during their birth hospitalizations have significantly longer length of stay and are more likely to develop chronic respiratory disease, particularly bronchopulmonary dysplasia (Bennett et al., J Pediatr 161:814–818, 2012). Furthermore, infants with RVIs are often placed on empiric antibiotic therapy, which can frustrate antimicrobial stewardship efforts (Bennett et al., J Pediatr 161:814–818, 2012; Cantey et al., Lancet Infect Dis 2016;16:1178–1184). RVIs are also associated with increased costs to both health systems and families due to increased care and lost productivity. In 2016, Zinna et al. (Pediatrics 138:e20161675, 2016) showed that infants with hospital-acquired RVI in the United Kingdom had hospital charges more than double those of uninfected infants. Similarly, the Sentinel-1 Study (Anderson et al., Am J Perinatol 34:51–61, 2017) in the United States demonstrated that each hospitalization for respiratory syncytial virus (RSV), the most common etiological agent of viral bronchiolitis in children age <1 year, costs more than $55,000, even excluding the additional outpatient visits before and after hospitalization. The goal of this chapter is to address the epidemiology, pathogenesis, diagnosis, treatment, and prevention of respiratory viruses in the highly vulnerable patient population in the NICU.


title: Bioterrorismus, infektiologische Aspekte

text: Infektionskrankheiten sind ständige Begleiter und gefürchtete Geißeln der Menschheit. Pest und Pocken versetzen als todbringende Seuchen die Menschen nicht erst seit dem Altertum in Schrecken (lat.: terror). Archaische Ängste und vor allem eine hohe Medienaufmerksamkeit sorgen immer wieder für Panik und irrationale Reaktionen: Im indischen Surat setzte im Herbst 1994 während eines ungewöhnlichen Pestausbruchs eine Massenflucht ein, nachdem die Presse den Verdacht auf Lungenpest und terroristische Anschläge verbreitet hatte. Über 800.000 Menschen, darunter auch zahlreiche Ärzte und Pflegekräfte, verließen daraufhin ihre Arbeitsplätze und Wohnorte. Allein die drastischen Flug- und Handelsbeschränkungen brachten Indien einen ökonomischen Schaden von etwa 3 Milliarden US $.


title: Chirurgische Infektionen bei Kindern und Jugendlichen

text: Der menschliche Organismus ist von einer unzähligen Menge von Mikroorganismen umgeben. Dringen diese Krankheitserreger in uns ein, dann laufen Wechselbeziehungen zwischen dem Eindringling und dem Wirtsorganismus ab. Krankheit resultiert, wenn die Mikroorganismen aufgrund ihrer verschiedenen Determinanten der Pathogenität und Virulenz den Wettlauf mit der Infektabwehr des Makroorganismus gewonnen haben. Mit diesem Problem hatten sich Chirurgen zu allen Zeiten auseinanderzusetzen und es hat bis heute nicht an Aktualität verloren.


title: Mobile Phone Media and Its Public Opinion Management

text: This chapter mainly discusses the concept, characteristics and cases of the mobile media and mobile media public opinion as well as their management, and lays stress on studying the development and characteristics of WeChat, the major social media and mobile payment platform in China.


title: Blood Products

text: Perioperative hemorrhage, anemia, thrombocytopenia, and coagulopathy are common in the surgical intensive care unit. As a result, blood product transfusion occurs frequently. While red blood cell, plasma, and platelet transfusions have a lifesaving role in the resuscitation of patients with trauma and hemorrhagic shock, their application in other settings is under scrutiny. Current data would suggest a conservative approach be taken, thus avoiding unnecessary transfusion and associated potential adverse events. New and developmental products such as prothrombin complex concentrates offer appealing alternatives to traditional transfusion practice—potentially with fewer risks—however, further investigation into their safety and efficacy is required before practice change can take place.


title: Indoor Microbial Aerosol and Its Health Effects: Microbial Exposure in Public Buildings – Viruses, Bacteria, and Fungi

text: Mechanisms of aerosolization of microorganisms, composition and dynamics of microbioaerosol are characterized. As well as methods of its detection, incl. modern equipment set-ups and sampling procedures recommended are outlined. Medical impact of (indoor) air disperged viral, bacterial and fungal propagules (allergies, intoxications, infections), together with the related European legislation is summarized. An overview of real mycoaerosol conditions in our dwellings and their outdoors with different microclimate, settlement and building types, household characteristics and health state of occupants is given, too. Finally, examples of several possible health damages due to exposition to (aerosolized) fungal toxicants in vitro and in vivo are demonstrated.


title: Neonatal Care and Data

text: Neonatology encompasses the care of all infants: from term newborns to extremely premature infants, from healthy infants to those suffering from severe infections or genetic disorders. While the management of infants can vary greatly, there are essential core data and knowledge that is needed to care for them.


title: Respiratory Disorders

text: This chapter provides the reader with a concise outline of the topics required for general pediatric board examination, respiratory component. Basic diagnostic testing is reviewed. Common upper airway problems, lower airway issues, and parenchymal diseases are covered. Congenital malformations and common diseases of the lung are reviewed. The physiology of extrapulmonary problems is reviewed. Sleep disordered breathing and the evaluation of apneas and ALTE/SIDS are also discussed. Hints regarding physiology, clinical features, diagnostic testing, and management are present with references to national guidelines and resources.


title: In the Midst of Stories: Is Seeing Believing?

text: In this chapter, the author explores issues and challenges in the narrative inquiry into Chinese families’ lived experience on landscapes of schools in transition from China to Canada. Entering the research field, the issue of narrative truth became a methodological challenge as the researcher was bounced between the boundaries of educational research. By understanding story as the phenomenon, and narrative as the inquiry (Clandinin & Connelly, Narrative inquiry: Experience and story in qualitative research, Jossey-Bass Publishers, San Francisco; 2000), the researcher asked two questions when she was located in a place of stories: “Who tells whose stories and why?” and “Which is true, ‘To see is to believe’, or ‘To believe is to see’?” In this methodologically focussed chapter ethical issues and considerations are also discussed.


title: Hierarchical Self-Assembled Peptide Nano-ensembles

text: A variety of peptides can be self-assembled, i.e. self-organized spontaneously, into large and complex hierarchical structures, reproducibly by regulating a range of parameters that can be environment driven, process driven, or peptide driven. These supramolecular peptide aggregates yield different shapes and structures like nanofibers, nanotubes, nanobelts, nanowires, nanotapes, and micelles. These peptide nanostructures represent a category of materials that bridge biotechnology and nanotechnology and are found suitable not only for biomedical applications such as tissue engineering and drug delivery but also in nanoelectronics.


title: A Virus from the Nile

text: It probably happened in August. Beyond that, no one can say when the tiny brown wisp settled upon Enrico Gabrielli’s body. The sixty-year-old cherished summer evenings among the red geraniums and purple cosmos in his garden, in the Italian neighborhood of Whitestone in Queens, New York— and never more so than in the summer of 1999. In July the temperature broke ninety-five degrees for eleven straight days—the hottest month ever recorded in the city.


title: Models for Endemic Diseases

text: We have been studying SIR models, in which the transitions are from susceptible to infective to removed, with the removal coming through recovery with full immunity (as in measles) or through death from the disease (as in plague, rabies, and many other animal diseases). Another type of model is an SIS model in which infectives return to the susceptible class on recovery because the disease confers no immunity against reinfection. Such models are appropriate for most diseases transmitted by bacterial or helminth agents, and most sexually transmitted diseases (including gonorrhea, but not such diseases as AIDS, from which there is no recovery). One important way in which SIS models differ from SIR models is that in the former there is a continuing flow of new susceptibles, namely recovered infectives. Later in this chapter we will study models that include demographic effects, namely births and deaths, another way in which a continuing flow of new susceptibles may arise.


title: Colostrum Antibodies, Egg Antibodies and Monoclonal Antibodies Providing Passive Immunity for Animals

text: Passive immunity can be provided to animals by several sources of antibodies including from colostrum, avian eggs, and monoclonal sources. These antibodies have been shown protect production and companion animals from a number of pathogens. This chapter reviews the immune system for the principles of immune response to antigens and the synthesis of immunoglobulins of the five classes of antibodies in the body. Colostrum antibodies are described for passive immunity protection in animals such as calves. Chicken egg antibodies are another source of antibodies for passive immunity. Therapeutic monoclonal antibodies are also used to provide passive immunity in the veterinary field.


title: Hydrocephalus in Animals

text: Naturally occurring internal hydrocephalus is diagnosed in all kinds of mammals including exotic species as well as in birds. The underlying pathomechanisms are extremely variable and species-specific. In ruminants, teratogenic viruses are the main underlying cause for congenital hydrocephalus. Intrauterine infections do not play a role in equids, and the site of obstruction of CSF flow typically remains undetermined. In birds and large felids, hydrocephalus is usually acquired and often associated with vitamin A deficiency. In dogs and cats, it can be congenital but also associated with impaired skull and vertebral growth. Reduced cranial capacity impairing cerebral compliance and malformations of the craniovertebral junction (atlantoaxial instability, occipito-atlantoaxial overlap syndrome, and “Chiari-like malformation”) are the most common causes for an impaired CSF flow and communicating hydrocephalus in a high number of brachycephalic breeds. With increasing knowledge and the increasing disposition of patient owners, veterinary specialists and researchers enduringly invest in the patient management; ventriculoperitoneal shunting techniques have become a reasonable treatment strategy in dogs.


title: Effekte technologischer Angebotsschocks

text: Das Wachstum der Gesundheitswirtschaft in Deutschland ist von einer überdurchschnittlich starken Dynamik geprägt. Beleg hierfür sind die Entwicklungen makroökonomischer Kennzahlen wie die Anzahl der Erwerbstätigen und der Bruttowertschöpfung im Zeitablauf. In den Jahren 2007–2012 entspricht die durchschnittliche Wachstumsrate der gesamtwirtschaftlichen Bruttowertschöpfung einem Wert von 2,3 Prozent; im selben Zeitraum ist die Gesundheitswirtschaft jahresdurchschnittlich mit 3,7 Prozent deutlich schneller gewachsen (vgl. BMWi 2013, S. 4).


title: Illustrationsbeispiel „Grenzwerte für Schadstoffe im Wasser“

text: Zu Beginn möchte ich versuchen, auf die konkrete Problematik eines im Januar 2012 veröffentlichten Entwurfs einer EU-Verordnung mit Veränderungen der Grenzwerte für Schadstoffe im Wasser einzugehen.


Pneumonia and Empyema


Bombs, Mines, Blast, Fragmentation, and Thermobaric Mechanisms of Injury


title: Pneumonie

text: Die maximale Inzidenz von ventilatorassoziierter Pneumonie (VAP) liegt nach Ibrahim et al. (2001) zwischen dem 6. und dem 10. Tag (◘ Abb. 13.1).


title: Global Mass Society

text: Economic globalization has resulted in corporations, unaccountable to states, making key decisions within an otherwise anarchic world order, rendering normal democratic functioning almost impossible. Global gridlock has resulted from the same issues that plague democracies today. Although transnational civil society has tried to achieve a degree of democratic global governance, the result mostly has been to reinforce the global power structure.


title: Evolution of Intensive Care Unit Nursing

text: The specialties of critical care medicine and critical care nursing arose to provide special treatment and care to the most severely ill hospital patients. However, critical care medicine does not seem to have made any major therapeutic progress in the past 30 years. The reduction of mortality in intensive care units (ICUs) is due essentially to improvements in both supportive care and the relevant technologies. In future, increases in the number of ICU beds relative to bed numbers in other hospital wards will probably be contemplated, even in a scenario of decreasing costs; clinical protocols will be computerized and/or nurse-driven; more multicenter and international trials will be performed; and organizational strategies will concentrate ICU personnel in a few large units, to promote the flexible management of these healthcare workers. Moreover, extracorporeal organ support technologies will be improved; technology informatics will cover all the bureaucratic aspects of healthcare work, aiding the staff in workload assessment; and critical care multidisciplinary rounds and follow-up services for post-ICU patients will be implemented. Lastly, a better continuum of care between the pre-hospital phase, the emergency care phase, the ICU phase, and the post-ICU phase should be achieved. Also, policies should be drafted to manage sudden large demands for critical care beds in mega-emergencies. The main lines of discussion in critical care nursing research should include nursing research priorities in critical care patients, holistic approaches to the patient, the humanization of care, special populations of ICU patients, and challenges related to critical care nursing during emerging outbreaks of infectious diseases.


title: Aviation and Intervention

text: In October 2013, CNN reported that 400 civilians had been killed in Pakistan by unmanned aircraft (UA) since President Obama took office in 2009. Transnational legal theory suggests that such attacks are illegal and, in 2009, the United Nations special rapporteur on extra judicial killings suggested that the use of drones by the Obama administration in Afghanistan and Pakistan was untenable and contrary to international law.


title: Anesthesia Management of Liver Transplantation

text: Anesthesia for liver transplantation pertains to a continuum of critical care of patients with end-stage liver disease. Hence, anesthesiologists, armed with a comprehensive understanding of pathophysiology and physiologic effects of liver transplantation on recipients, are expected to maintain homeostasis of all organ function. Specifically, patients with fulminant hepatic failure develop significant changes in cerebral function, and cerebral perfusion is maintained by monitoring cerebral blood flow and cerebral metabolic rate of oxygen, and intracranial pressure. Hyperdynamic circulation is challenged by the postreperfusion syndrome, which may lead to cardiovascular collapse. The goal of circulatory support is to maintain tissue perfusion via optimal preload, contractility, and heart rate using the guidance of right-heart catheterization and transesophageal echocardiography. Portopulmonary hypertension and hepatopulmonary syndrome have high morbidity and mortality, and they should be properly evaluated preoperatively. Major bleeding is a common occurrence, and euvolemia is maintained using a rapid infusion device. Pre-existing coagulopathy is compounded by dilution, fibrinolysis, heparin effect, and excessive activation. It is treated using selective component or pharmacologic therapy based on the viscoelastic properties of whole blood. Hypocalcemia and hyperkalemia from massive transfusion, lack of hepatic function, and the postreperfusion syndrome should be aggressively treated. Close communication between all parties involved in liver transplantation is also equally valuable in achieving a successful outcome.


title: Reintroduction

text: The introduction presents the concepts of health in relation to order, disorder, and re-ordering. It defines health and the right to health along with the concomitant responsibilities for its realization ascribed to nation-state and non-state actors. It discusses the remit of health security as the provision and protection of health rights through responsibilities at the local, national, and global levels of community and governance. Finally, it argues that health risks and threats cannot be completely eliminated, but rather must be identified and responded to in a coordinated manner involving individuals, communities, national states, international organizations, and the global (conceptual) community.


title: SARS and H5N1

text: Chapter 5 looks at bird flu (H5N1) pandemics and Severe Acute Respiratory Syndrome (SARS). This chapter shifts the focus from the relationship between individual health rights and state requirements, notably immunization, and responsibilities, particularly in providing security against health threats, to international requirements and responsibilities for health. Through the lens of the SARS and the H5N1, it traces the newest evolution of the International Health Regulations (IHRs). It analyses the positions and compromises of states, notably with regard to their sovereignty, in reaching the final compromise: to share responsibility in safeguarding global health. It takes to task the regulations’ lack of ‘teeth’: the fact that despite international treaty status, the IHRs operate on a voluntary basis without an enforcement mechanism.


title: Human metapneumovirus infection

text: Initially, human metapneumovirus (hMPV) was isolated from children with clinical symptoms of respiratory syncytial virus (RSV) infection in whom RSV could not be detected. Since then, numerous reports have described the detection of hMPV in clinical specimens from children, adults and the elderly (both immunocompetent and immunocompromised patients), diagnosed with an acute respiratory illness all over the world. hMPV is associated with a substantial number of respiratory tract infections in otherwise healthy children, with clinical illnesses similar to those associated with other common respiratory viruses. Serological surveys have shown that hMPV is a ubiquitous virus that infects all children by the age of 5–10 years and has been circulating in humans for at least 50 years. hMPV is a member of the Metapneumovirus genus of the Paramyxoviridae family, a group of negative-stranded RNA viruses. Genetic studies on hMPV have demonstrated the presence of two distinct hMPV serotypes each divided in two subgroups. Diagnosis is made by RT-PCR assays on respiratory secretions. Rapid antigen detection tests are not yet available and its growth in cell cultures is fastidious. No vaccines, antibodies (monoclonal or polyclonal), or chemotherapeutic agents are currently licensed for use to prevent or treat hMPV infections. The contribution of hMPV to pediatric respiratory tract infections suggests that it will be important to develop a vaccine against this virus in combination with those being developed for RSV and parainfluenza viruses. Reverse genetics technology is currently used to develop multivalent vaccines against hMPV and a variety of other important respiratory viruses such as RSV. Additional research to define the pathogenesis of this viral infection and the host’ specific immune response will enhance our knowledge to guide the search for preventive and therapeutical strategies.


title: Stem Cell Therapy in the Treatment of Rheumatic Diseases and Application in the Treatment of Systemic Lupus Erythematosus

text: Current systemic therapies help to improve the symptoms and quality of life for patients with severe life-threatening rheumatic diseases but provide no curative treatment. For the past two decades, preclinical and clinical studies of stem cell transplantation (SCT) have demonstrated tremendous therapeutic potential for patients with autoimmune rheumatic diseases. Herein, the current advances on stem cell therapies, both in animal models and clinical studies, are discussed, with particular attention on systemic lupus erythematosus (SLE). Despite extensive research and promising data, our knowledge on mechanisms of action for SCT, its administration route and timing, the optimal dose of cells, the cells’ fate and distribution in vivo, and the safety and efficacy of the treatments remains limited. Further research on stem cell biology is required to ensure that therapeutic safety and efficacy, as observed in animal models, can be successfully translated in clinical trials. Current understanding, limitations, and future directions for SCT with respect to rheumatic diseases are also discussed.


title: Introduction: A Prelude to Mathematical Epidemiology

text: Recorded history continuously documents the invasion of populations by infectious agents, some causing many deaths before disappearing, others reappearing in invasions some years later in populations that have acquired some degree of immunity, due to prior exposure to related infectious pathogens. The “Spanish” flu epidemic of 1918–1919 exemplifies the devastating impact of relatively rare pandemics; this one was responsible for about 50,000,000 deaths worldwide, while on the mild side of the spectrum we experience annual influenza seasonal epidemics that cause roughly 35,000 deaths in the USA each year.


title: Rhinovirus, Coronavirus, Enterovirus, and Bocavirus After Hematopoietic Cell Transplantation or Solid Organ Transplantation

text: Respiratory viral infections represent a significant cause of morbidity and mortality in immunocompromised hosts. Newer molecular detection assays have allowed for the characterization of several respiratory viruses not previously recognized as having significant clinical impact in the immunocompromised population. Human rhinoviruses are the most common respiratory viruses detected in the upper respiratory tract of hematopoietic cell transplant and lung transplant recipients, and evidence on the impact on clinical outcomes is mounting. Other respiratory viruses including enteroviruses (EVs), coronaviruses (CoVs), and bocavirus may also contribute to pulmonary disease; however, data is limited in the immunocompromised population. Further studies are needed to define the epidemiology, risk factors, and clinical outcomes of these infections; this data will help inform decisions regarding development of antiviral therapy and infection prevention strategies.


title: Applied Bioinformatics Tools

text: A hands-on course mainly for the applications of bioinformatics to biological problems was organized at Peking University. The course materials are from http://abc.cbi.pku.edu.cn. They are divided into individual pages (separated by lines in the text):


title: New and Re-Emerging Infectious Diseases in Sub-Saharan Africa

text: Over the past 30 years, Africa has achieved significant health gains. Life expectancy has risen while infant, child, and maternal mortality have declined. Despite these improvements, the continent still faces serious challenges from infectious diseases. The chapter covers HIV and AIDS and other epidemics in sub-Saharan Africa. It addresses the origins, evolution, mortality, morbidity, and socio-economic impacts of the epidemics, as well as the policies and programs put in place to combat them. The chapter concludes with a review of the funding and the sustainability of such financial efforts.


title: A Young Adult with Cough and Wheezing Since Infancy

text: A 20-year-old man presented for outpatient evaluation of treatment options for recurrent respiratory papillomas. He was born with vocal cord paralysis. At 4 weeks of life, he underwent tracheostomy. In childhood his tracheostomy was closed, and he was found to have occasional, small papillomas in the trachea. During puberty, he experienced a dramatic increase in the number and size of the papillomas.


title: Colonization of Parasites and Vectors

text: Colonization comprises the physical arrival of a species in a new area, but also its successful establishment within the local community. Oceanic islands, like the Hawaiian and the Galapagos archipelagos, represent excellent systems to study the mechanisms of colonization because of their historical isolation. In this chapter, we first review some of the major mechanisms by which parasites and vectors could arrive to an oceanic island, both naturally or due to human activities, and the factors that may influence their successful establishment in the insular host community. We then explore examples of natural and anthropogenic colonization of the Galapagos Islands by parasites and vectors, focusing on one or more case studies that best represent the diversity of colonization mechanisms that has shaped parasite distribution in the archipelago. Finally, we discuss future directions for research on parasite and vector colonization in Galapagos Islands.


Antibody Phage Display


Pneumologie


title: Secondary Metabolite Production in Transgenic Hairy Root Cultures of Cucurbits

text: Cucurbits are important group of vegetables due to their nutritional significance and are also used for valuable traditional medicine. The infection of plants by Agrobacterium rhizogenes results in a hairy root (HR) phenotype characterized by rapid growth in hormone-free medium, an unusual ageotropism and extensive lateral branching. These genetically transformed root cultures (hairy roots) can produce levels of secondary metabolites comparable to that of intact plants. Hairy root cultures offer promise for high production and productivity of valuable secondary metabolites in many plants. High stability and productivity features allow the exploitation of HRs as valuable biotechnological tool for the production of plant secondary metabolites. While these chemical compounds are employed by plants for interactions with their environment, humans have long since explored and exploited plant secondary metabolites for medicinal and practical uses. The main constraint for commercial exploitation of hairy root cultivations is the development and scaling up of appropriate reactor vessels (bioreactors) that permit the growth of interconnected tissues normally unevenly distributed throughout the vessel. Emphasis has focused on designing appropriate bioreactors suitable to culture the delicate and sensitive plant hairy roots. To this end, hairy root culture presents an excellent platform for producing valuable secondary metabolites. For these reasons, this chapter describes the establishment of hairy roots and production of secondary metabolites from hairy roots of cucurbits and also phytochemicals uses for biological activity.


title: Biological and Chemical Weapons

text: The five anthrax letters put in the US mail in 2001 greatly raised concerns about BW and CW. In general, chemical weapons are considered about as lethal per unit mass as conventional explosives and much less lethal than either nuclear or biological weapons (dirty bombs are much less lethal, Chap. 10.1007/978-3-319-25367-1_13). Biological weapons can be as lethal as nuclear weapons if dispersed effectively, but that is not easy to do. For BW to be effective, the bio-materials must be chemically robust, remaining stable, not decaying in sunlight, moisture and rain. This can be accomplished with spores and aerosols. BW material must be dispersed widely, not clumping in few locations. BW can be delivered by cluster bomblets from small missiles. BW can be delivered by helicopter or low-flying crop-duster, or BW can be released in many locations in many small spray cans.


title: Myocarditis

text: Viruses are the most common cause of myocarditis in economically advanced countries. Enteroviruses and adenoviruses are the most common etiologic agents. Viral myocarditis is a triphasic process. Phase 1 is the period of active viral replication in the myocardium during which the symptoms of myocardial damage range from none to cardiogenic shock. If the disease process continues, it enters phase 2, which is characterized by autoimmunity triggered by viral and myocardial proteins. Heart failure often appears for the first time in phase 2. Phase 3, dilated cardiomyopathy, is the end result in some patients. Diagnostic procedures and treatment should be tailored to the phase of disease. Viral myocarditis is a significant cause of dilated cardiomyopathy, as proved by the frequent presence of viral genomic material in the myocardium, and by improvement in ventricular function by immunomodulatory therapy. Myocarditis of any etiology usually presents with heart failure, but the second most common presentation is ventricular arrhythmia. As a result, myocarditis is one of the most common causes of sudden death in young people and others without preexisting structural heart disease. Myocarditis can be definitively diagnosed by endomyocardial biopsy. However, it is clear that existing criteria for the histologic diagnosis need to be refined, and that a variety of molecular markers in the myocardium and the circulation can be used to establish the diagnosis. Treatment of myocarditis has been generally disappointing. Accurate staging of the disease will undoubtedly improve treatment in the future. It is clear that immunosuppression and immunomodulation are effective in some patients, especially during phase 2, but may not be as useful in phases 1 and 3. Since myocarditis is often selflimited, bridging and recovery therapy with circulatory assistance may be effective. Prevention by immunization or receptor blocking strategies is under development. Giant cell myocarditis is an unusually fulminant form of the disease that progresses rapidly to heart failure or sudden death. Rapid onset of disease in young people, especially those with other autoimmune manifestations, accompanied by heart failure or ventricular arrhythmias, suggests giant cell myocarditis. Peripartum cardiomyopathy in economically developed countries is usually the result of myocarditis.


title: Misguided Responses to Public Health Emergencies

text: This chapter considers some misguided responses to public health emergencies, or perceived emergencies. At one extreme was the arrest and lifetime confinement in Hawaii and elsewhere of sufferers from leprosy, or Hansen’s disease. This, of course, was not an example of presidential policy, but is included as an example of horrible overreach. An opposite approach was the refusal of the Eisenhower administration to mount a vaccination program to deal with the Asian flu pandemic of 1957. President Eisenhower was devoted to private solutions to such emergencies, and these were manifestly inadequate. There was yet another extreme example of a misguided approach, and that was President Woodrow Wilson’s militant passivity to the 1918 influenza pandemic. Disregarding advice from medical consultants, he refused to discontinue the shipment of troops abroad to fight in the Great War, which resulted in an even greater spread of the contagion because of the great numbers of men confined to small quarters aboard ships. Incompetence can always be a danger in public health emergencies. Although this was not a pandemic, the George W. Bush administration handled the health crisis caused by Hurricane Katrina so poorly that it became a national scandal. On the other hand, President Bush did move to plan wisely for a possible influenza pandemic when he ordered the creation of national stockpiles of antiviral medication.


Laboratory Diagnosis of Viral Disease


title: Infectious Diseases Prevention and Control

text: China is a big country with huge regional differences in social economic development. The large population, high population density and mobility, as well as significant regional differences in life style make infectious diseases a major threat to China. With strong outburst and fast spread, infectious diseases are also more difficult to control in China. So China has to stick to a strategy which emphasizes both prevention and therapy in infectious disease control.


title: DLI Induced by Herbal Medicine: What Are the Characteristics of DLI due to Herbal Medicines?

text: In many countries, herbal medicine has been developed and is currently practiced. Herbal medicine involves the use of the stalks, roots, leaves, flowers, and berries of several different plant species for medical treatment. Many practitioners believe that herbal medication has no side effects because of its natural origin. Thus, herbal medication has been used for a long time with little awareness of its side effects. However, there is an increasing incidence of interstitial pneumonia due to a drug-induced lung injury (DLI), which could be induced by common drugs. Moreover, increasing cases of bronchiolitis obliterans and pulmonary hypertension are being reported; further, these are drug-induced conditions. Clinicians should be more aware of DLI symptoms caused by herbal medication and interrogate patients regarding their use of herbal medication and supplements as well as prescription drugs.


title: Collectivism–Individualism, Family Ties, and Philopatry

text: As predicted by the parasite-stress theory of values, variation in parasite stress correlated with collectivism–individualism across nations, USA states, and indigenous societies. In regions with high adversity of infectious diseases, human cultures are characterized by high collectivism, whereas in regions of low parasite stress cultures are highly individualistic. The prediction from the parasite-stress theory of values that infectious disease transmissible among humans (nonzoonotics) will be more important in predicting collectivism–individualism than those that humans can contract only from nonhuman animals (zoonotics) was supported. Evidence in human movement patterns for nations, states of the USA, and indigenous societies supports the hypothesis that the absence of dispersal (high philopatry) is a defense against contact with novel parasites in out-groups and their habitats. We show that human cultures with high degrees of collectivism have high degrees of cooperative breeding, and propose that the parasite-stress theory of sociality offers a general theory of family structure across humans as well as nonhuman animal taxa. We propose that a major context for the evolution of human reciprocity was in gaining benefits from out-group interactions during periods of relatively low disease threat. The parasite-stress theory of values offers a novel perspective to explain the evolution of reciprocity and human unique cognitive abilities. The parasite-stress theory suggests useful new research directions for the study of the demographic transition, patriotism, xenophobia, ethnocentrism, and moral foundations theory. We include discussion of ecological correlations and the ecological fallacy. The fact that all scientific findings are correlational is explained.


title: Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview

text: The chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) are important mediators of leukocyte trafficking in inflammatory processes. The emerging evidence for a role of CCR2 and CCR5 receptors in human inflammatory diseases led to a growing interest in CCR2- and CCR5-selective antagonists. In this review, we focus on the recent development of selective CCR2/CCR5 receptor ligands and dual antagonists. Several compounds targeting CCR2, e.g., INCB8761 and MK0812, were developed as promising candidates for clinical trials, but failed to show clinical efficacy as presumed from preclinical models. The role of CCR5 receptors as the second co-receptor for the HIV-host cell fusion led to the development of various CCR5-selective ligands. Maraviroc is the first CCR5-targeting drug for the treatment of HIV-1 infections on the market. The role of CCR5 receptors in the progression of inflammatory processes fueled the use of CCR5 antagonists for the treatment of rheumatoid arthritis. Unfortunately, the use of maraviroc for the treatment of rheumatoid arthritis failed due to its inefficacy. Some of the ligands, e.g., TAK-779 and TAK-652, were also found to be dual antagonists of CCR2 and CCR5 receptors. The fact that CCR2 and CCR5 receptor antagonists contribute to the treatment of inflammatory diseases renders the development of dual antagonists as promising novel therapeutic strategy.


title: Taxonomy

text: This chapter addresses the classification and taxonomy of viruses with special attention to viruses that show pneumotropic properties. Information provided in this chapter supplements that provided in other chapters in Parts II–V of this volume that discuss individual viral pathogens.


title: Searching for Superspreaders: Identifying Epidemic Patterns Associated with Superspreading Events in Stochastic Models

text: The importance of host transmissibility in disease emergence has been demonstrated in historical and recent pandemics that involve infectious individuals, known as superspreaders, who are capable of transmitting the infection to a large number of susceptible individuals. To investigate the impact of superspreaders on epidemic dynamics, we formulate deterministic and stochastic models that incorporate differences in superspreaders versus nonsuperspreaders. In particular, continuous-time Markov chain models are used to investigate epidemic features associated with the presence of superspreaders in a population. We parameterize the models for two case studies, Middle East respiratory syndrome (MERS) and Ebola. Through mathematical analysis and numerical simulations, we find that the probability of outbreaks increases and time to outbreaks decreases as the prevalence of superspreaders increases in the population. In particular, as disease outbreaks occur more rapidly and more frequently when initiated by superspreaders, our results emphasize the need for expeditious public health interventions.


title: Pathogenesis of COPD (Persistence of Airway Inflammation): Why Does Airway Inflammation Persist After Cessation of Smoking?

text: The structural features of airways in patients with COPD are airway wall inflammation, fibrosis, muscle hypertrophy, and goblet cell metaplasia. These structural cellular changes contribute to mucus hypersecretion and destruction of the alveolar walls and a decline in forced expiratory volume in one second (FEV(1)). At the cellular level, macrophages, T lymphocytes, and neutrophils, driven by cytokines including interleukin-8 (IL-8), gather on the airways. The main cause of COPD inflammation is cigarette smoke. Smoke causes an increase in the secretion of matrix metalloproteinase (MMPs) and neutrophilic elastase from epithelial cells and neutrophils, which are responsible for mucin production and destruction of the lung. Initially, cigarette smoke influences the expression of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), the intracellularly located nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and receptors for advanced glycation end products (RAGE) on lung epithelial cells, endothelial cells, and leukocytes in the lung. These actions bring about the production of cytokines and activation of inflammatory cells, leading to production of MMPs and neutrophilic elastase. The inflammatory changes persist for several months and years after smoking cessation and are sometimes irreversible. Damage-associated molecular patterns (DAMPs) released from dying cells after cigarette smoking increase the number of apoptotic cells, suppress efferocytosis, induce hypoxia and oxidative stress, and prolong the inflammatory changes, even after smoking cessation. Viral and bacterial infections of the respiratory tract then fortify these inflammatory responses. Exacerbations of COPD then worsen the deterioration of COPD.


When a Diagnosis Is Reportable


title: Emerging Viruses

text: Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs.