title: Killing More than Pain: Etiology and Remedy for an Opioid Crisis

text: The search for effective pain relief has been ever present across human history. The discovery of opium’s ability to relieve pain stimulated the refinement of opium and generation of synthetic analogues to create more effective, potent, and faster-acting analgesics. The social and economic value of opioids has remained high not only due to their demonstrated efficiency in mitigating pain but also their noteworthy ability to reliably produce rewarding psychological effects. Consequently, at various times during the past several hundred years, opioids have sparked wars, fueled black markets and cartel crime, and triggered numerous opioid addiction and overdose death epidemics around the world. The increased therapeutic desire to address pain together with pharmaceutical discoveries in medication design, rapid manufacture, and highly effective opioid marketing and distribution has led more recently to increased availability and accessibility to potent prescription opioids, which has sparked the deadliest overdose crisis in human history. This chapter describes the etiology and epidemiology of the opioid crisis using public health and Health Belief Model frameworks and reviews approaches that have been applied to address supply (e.g., overprescribing) and demand (e.g., medication treatments) sides of the equation. Causes of the growth and spread of the overdose epidemic are analyzed as a way to inform a successful end to the current crisis as well as to prevent future epidemics.


title: Airway Anatomy, Physiology, and Inflammation

text: Approximately 10,000 l of air and 8,000 l of blood transit the respiratory system each day driven by small pressure gradients developed in response to rhythmic contraction and relaxation of striated muscle under both voluntary and involuntary control of the central nervous system. Matching of air- and blood flow results from central and local reflexes responding to both internal and external stimuli and subsequently controlling the pumps, as well as the smooth muscle in walls of the airways and blood vessels. A wide range of neural and immune mechanisms protect the lungs against environmental insults, and many are adaptive in nature, resulting in memory that increases sensitivity and responsiveness upon repeated exposure to stimuli. In over 10 % of the population, the responses to environmental stimuli become pathological, resulting in excessive sensitivity and aberrant responses to both specific and nonspecific stimuli, and culminate in physical remodeling of the airways and lungs. Prevention, definitive diagnosis, and effective treatment of the disorders require a better understanding of the mechanisms underlying excessive responses to environmental stimuli.


title: Medical Management of Acute Rhinosinusitis in Children and Adults

text: Acute rhinosinusitis is a commonly seen disease that is frequently diagnosed based on clinical symptomatology without any objective evidence. The most common form of treatment is antibiotics, even though many cases may not have a bacterial etiology. The most common bacterial organisms in childhood sinusitis belong to the group that cause many childhood upper respiratory and lower respiratory infections and include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Besides antibiotics, other treatments are aimed at assisting with drainage, and this can be accomplished by reducing the inflammation and edema that prevents venting of the sinus structures. These medications can include antihistamines, decongestants, intranasal steroids, nasal saline irrigation, and, in some countries, mucolytics. Complementary and alternative medicine (CAM) techniques including Chinese herbal medications are often used, but there is little scientific evidence to support their use. The use of immunotherapy has not been found to be effective in the management of acute rhinosinusitis in children or adults.


title: Haut und Tiere

text: Tiere spielen in der Pathogenese zahlreicher Hautkrankheiten eine bedeutende Rolle. Für den Hautarzt sind klinische Angaben zu vorausgegangenem Tierkontakt von großer klinischer und differenzialdiagnostischer Bedeutung. Tiere können als Vektoren gefährlicher pathogener Krankheitserreger wie Viren, Bakterien, Protozoen, Pilze und Würmer fungieren, Ektoparasiten auf die Haut übertragen, selbst auf beziehungsweise in der Haut parasitieren, aber auch durch Tierallergene und Toxine lokale kutane Intoleranzreaktionen, systemische toxische sowie anaphylaktische Reaktionen mit tödlichem Ausgang herbeiführen [9, 43, 111, 114]


title: Cancer of Reproductive System: Receptors and Targeting Strategies

text: Carcinogenesis in the different organs of the reproductive system, particularly, prostate, ovarian, and cervical tissues, involves aberrant expression of various physiological receptors belonging to different superfamilies. This chapter provides insights into the physiological receptors that are associated with the genesis, progression, metastasis, management, as well as the prognosis of the cancers of the male and female reproductive systems. It also highlights the structural and binding characteristics of the highly predominant receptors, namely, androgen, estrogen, progesterone, and gonadotropin-releasing hormone (GnRH) receptors, which are overexpressed in these cancers and discusses various strategies to target them.


title: Mechanisms of Acute Liver Failure

text: Acute liver failure (ALF) is characterized by the sudden onset of liver failure in a patient without evidence of chronic liver disease. This definition is important, as it differentiates patients with ALF from patients who suffer from liver failure owing to end-stage chronic liver disease [1].


title: Anesthesia for Open Abdominal Aortic Aneurysm Repair

text: Abdominal aortic aneurysms (AAAs) are the 13th leading cause of death in the United States 1 and approximately 40,000 patients undergo elective AAA repair each year.2 With the population aging, this number is expected to increase. Although the use of endovascular AAA repair is becoming more common, open repair, first reported by Dubost et al. in 1951 remains the gold standard.2 This chapter will review the etiology, risk factors, diagnosis, pathophysiology, operative technique, perioperative management, and postoperative complications of patients undergoing open AAA repair.


title: Hepatitis Delta Virus: HDV-HBV Interactions

text: The hepatitis delta virus (HDV) is a subviral agent that utilizes the envelope proteins of the hepatitis B virus (HBV) for cell to cell propagation. In infected human hepatocytes, the HDV RNA genome can replicate and associate with multiple copies of the delta protein to assemble a ribonucleoprotein (RNP). However the RNP cannot exit the cell because of the lack of an export system. This is provided by the HBV envelope proteins, which are capable of budding at an internal cellular membrane to assemble mature HDV virions when RNPs are present. This review covers advances in the molecular aspects of the HDV-HBV interactions, with an emphasis on the HBV properties that are instrumental in HDV maturation, in particular the central role of the small HBV envelope protein.


title: “Disease Knows No Borders”: Pandemics and the Politics of Global Health Security

text: Since the 1990s, the threat of pandemics has gained increased prominence on policy-makers’ agendas due to the emergence and resurgence of infectious diseases and an increasingly interconnected world. Encapsulated by the phrase “disease knows no borders,” this new risk environment has led to the rise of a new global health security regime, codified in the 2005 International Health Regulations. It is based on a paradigm of rapid detection and response to outbreak events, and on a norm of collective action. Drawing on examples from the 2014–2015 Ebola epidemic, we argue that pandemic preparedness is not just a technical matter, but also a political and normative one. We show that the global health security regime carries tensions that reflect asymmetries in actors’ capacities to put forward their priorities.


title: Shaping Ethical Guidelines for an Influenza Pandemic

text: This chapter describes the process of shaping ethical guidelines for an influenza pandemic by the North Carolina Institute of Medicine (NC IOM)/North Carolina Department of Public Health (NCDPH) Task Force. The author discusses the threat of a pandemic in the twenty-first century, comparing a potential pandemic with past flu pandemics as well as the Severe Acute Respiratory Syndrome (SARS) outbreak in Canada and parts of Asia. Also discussed are the ways in which influenza would spread, be treated, and hopefully contained. Addressed are the ways in which one becomes ethically prepared for an influenza pandemic, as well as the challenges to incorporating ethical guidelines in preparations. Tong also addresses the role of a duty/obligation/responsibility to work by health care personnel, the role of volunteers, and when health care personnel may refuse to treat someone. Also taken into consideration are such issues as the distribution of food and vaccines, quarantines, work stoppage, both physical and social infrastructure, the role of military and police forces, and the effect of a pandemic, isolation, and quarantine on various industries. Tong shows the complicated nature of working on a task force and the complexity of incorporating ethics into logistical planning.


title: Genomic and Postgenomic Research

text: The word genomics was first coined by T. Roderick from the Jackson Laboratories in 1986 as the name for the new field of science focused on the analysis and comparison of complete genome sequences of organisms and related high-throughput technologies.


title: Bakterielle Infektionen

text: Definition. Durch Staphylokokken verursachte Krankheiten können lokal begrenzt bleiben, generalisiert auftreten oder sich als Intoxikation äußern. Die frühere Einteilung der Staphylokokken nach der Produktion eines gelben Pigmentes in S. aureus und S. albus ist weitgehend verlassen worden. Wegen der Korrelation mit klinischen Krankheitsbildern hat sich dagegen die Einteilung der Staphylokokken in koagulasepositive (KPS) und koagulasenegative Staphylokokken (KNS) bewährt.


title: An Agent-Based Infectious Disease Model of Rubella Outbreaks

text: This study proposes a simulation model of rubella. SIR (Susceptible, Infected, Recovered) model has been widely used to analyse infectious diseases such as influenza, smallpox, bioterrorism, to name a few. On the other hand, agent-based model begins to spread in recent years. The model enables to represent the behaviour of each person on the computer. It also reveals the spread of infection by simulation of the contact process among people in the model. The study designs a model based on smallpox and Ebola fever model in which several health policies are decided such as vaccination, the gender-specific workplace and so on. The infectious simulation of rubella, which has not yet vaccinated completely for men in Japan, is implemented in the model. As results of experiments using the model, it has been found that preventive vaccine to all the men is crucial factors to prevent the spread in women.


title: Legionnaires’ Disease

text: The incidence of legionnaires’ disease (LD) seems to increase with age, particularly in males [36]. It was considered an infrequent cause of pneumonia in the past, but it currently ranks second to pneumococcus in the list of etiologic agents of severe community-acquired pneumonia (CAP) of bacterial origin [2, 24, 60, 89]. Considering less severe cases, in a series of 145 pneumonias in which BCYE culture, serology and the Legionella urinary antigen (LUA) test were systematically applied, Vergis et al. [91] reported a prevalence of LD of 13.7%. In another series of 392 adult patients with CAP treated in a university hospital, Sopena et al. found a prevalence of 12.5%, and LD was the second cause of pneumonia [83].


title: Compulsory Licences: Law and Practice in Thailand

text: When the WTO/TRIPS Agreement entered into force in 1995, around 100 countries had adopted compulsory licensing under national intellectual property law. The compulsory licensing measure can be effective in dealing with situations inhibiting access to medicines, for example when a patent holder fails to use the patent in the granting country or when he or she maintains artificially high prices for patented articles. Despite the significant international development, it remains to be seen how the flexibility margins provided by the TRIPS provisions can be used as safeguards to protect public health interests of the poor countries. Effective mechanisms are also required to support countries that are unable to make effective use of compulsory licensing due to the inefficiency of manufacturing capacity. This chapter examines the problem of using the legal mechanism of compulsory licensing by developing countries. It looks at Thailand’s experiences with the use of compulsory licensing to increase access to medicines. Since the majority of compulsory licences issued around the world are related to pharmaceutical patents, the chapter highlights the use of compulsory licensing in the context of a range of public health responses. It first discusses the use by Thailand of the compulsory government use licensing to increase access to medicines. It also examines international rules on compulsory licensing, including the provisions of the Paris Convention, the TRIPS Agreement, and the Doha Declaration on the TRIPS Agreement and Public Health. Finally, the chapter discusses various legal issues under the Thai Patent Act regarding the compulsory licensing provisions. It also highlights the possible impact, in a broad sense, of the use of legal mechanisms such as compulsory licensing, which aims to effectively maintain fair market competition and dilute the monopoly power of the patent holder.


title: Social Resilience and Critical Infrastructure Systems

text: Resilience analysis and thinking serve as emerging conceptual frameworks relevant for applications assessing risk. Connections between the domains of resilience and risk assessment include vulnerability. Infrastructure, social, economic, and ecological systems (and combined social-ecological systems) are vulnerable to exogenous global change, and other disturbances, both natural and anthropologically derived. Resilience analysis fundamentally seeks to provide the groundwork for a ‘soft landing’, or an efficient and robust restoration following disturbance as well as the ability to reduce harms while helping the targeted system rebound to full functionality as quickly and efficiently where possible. Such applications are consistent with The National Academy of Sciences (NAS) definition of resilience, which more broadly denotes the field as “the ability to plan and prepare for, absorb, recover from, and adapt to adverse events” (Larkin S, Fox-Lent C, Eisenberg DA, Trump BD, Wallace S, Chadderton C, Linkov I (2015) Benchmarking agency and organizational practices in resilience decision making. Environ Sys Decisions 35(2):185–195). Given this definition, we seek to describe how resilience analysis and resilience thinking might be applied to social considerations for critical infrastructure systems. Specifically, we indicate how resilience might better coordinate societal elements of such infrastructure to identify, mitigate, and efficiently recover from systemic shocks and stresses that threaten system performance and service capacity.


title: Acute Hepatic Failure

text: Acute liver failure (ALF) is an unpredictable and rapidly progressive, life-threatening multisystem condition that ensues when an insult causes diffuse necrosis of liver parenchyma disrupting hepatocyte function in patients who have no preexisting liver injury. The subsequent development of encephalopathy and coagulopathy within days or weeks represents the key features of ALF, but critically often culminates with multi-organ failure (MOF), which impacts significantly on mortality. Timely referral to specialist centres with expertise in the management of ALF and liver transplantation is crucial.


title: Equine Coronavirus Infection

text: Equine coronavirus (ECoV) is an emerging virus associated clinically and epidemiologically with fever, depression, anorexia, and less frequently colic or diarrhea in adult horses. Sporadic cases and outbreaks have been reported with increased frequency since 2010 from Japan, the USA, and more recently from Europe. A feco-oral transmission route is suspected, and clinical or asymptomatic infected horses appear to be responsible for direct and indirect transmission of ECoV. A presumptive clinical diagnosis of ECoV infection may be suggested by clinical presentation and hematological abnormalities such as leukopenia due to lymphopenia and/or neutropenia. Confirmation of ECoV infection is provided by specific ECoV nucleic acid detection in feces by quantitative PCR or demonstration of coronavirus antigen by immunohistochemistry or electron microscopy in intestinal biopsy material obtained ante- or postmortem. The disease is generally self-limiting and horses typically recover with symptomatic supportive care. Complications associated with disruption of the gastrointestinal barrier have been reported in some infected horses and include endotoxemia, septicemia, and hyperammonemia-associated encephalopathy. This chapter reviews current knowledge concerning the etiology, epidemiology, clinical signs, diagnosis, pathology, treatment, and prevention of ECoV infection in adult horses.


title: Conservation Medicine: A Solution-Based Approach for Saving Nonhuman Primates

text: Challenges that threaten the long-term survival of nonhuman primates (NHP) include habitat fragmentation, hunting, and increasingly, infectious diseases. In addition to direct mortality from noninfectious diseases (e.g., hunting) and infectious diseases (e.g., Ebola), human-driven alterations of environments that support NHP often contribute to a decline in population viability. This decline is frequently the result of physiological stress, poor reproduction, decreased immunity, and exposure to novel pathogens. To better understand the diseases that threaten NHP populations, a conservation medicine approach—the application of medicine to augment the conservation of wildlife and ecosystems—is imperative so that we may provide management solutions to help ensure the long-term survival of NHP. Additionally, it is crucial that we gain a better understanding of pathogens at the interface of nonhuman and human primates since the zoonotic potential may create conservation challenges, or alternatively may provide the impetus for conservation actions to be practiced (e.g., minimize bushmeat trade).


title: Miscellaneous Pulmonary Disease

text: In this chapter, a series of cases is presented that have provoked significant thought on the part of the consulting and consulted pathologists. Most of these cases don’t fall neatly into the context of other chapters in this volume. A number of these cases illustrate patterns of pulmonary disease that are not diagnostic and challenge the pathologist to offer an intelligent differential diagnosis. A brief discussion of some of these relevant diagnoses follows.


title: Incorporating Geographical Contacts into Social Network Analysis for Contact Tracing in Epidemiology: A Study on Taiwan SARS Data

text: In epidemiology, contact tracing is a process to control the spread of an infectious disease and identify individuals who were previously exposed to patients with the disease. After the emergence of AIDS, Social Network Analysis (SNA) was demonstrated to be a good supplementary tool for contact tracing. Traditionally, social networks for disease investigations are constructed only with personal contacts. However, for diseases which transmit not only through personal contacts, incorporating geographical contacts into SNA has been demonstrated to reveal potential contacts among patients. In this research, we use Taiwan SARS data to investigate the differences in connectivity between personal and geographical contacts in the construction of social networks for these diseases. According to our results, geographical contacts, which increase the average degree of nodes from 0 to 108.62 and decrease the number of components from 961 to 82, provide much higher connectivity than personal contacts. Therefore, including geographical contacts is important to understand the underlying context of the transmission of these diseases. We further explore the differences in network topology between one-mode networks with only patients and multi-mode networks with patients and geographical locations for disease investigation. We find that including geographical locations as nodes in a social network provides a good way to see the role that those locations play in the disease transmission and reveal potential bridges among those geographical locations and households.


title: Emerging and Re-emerging Infectious Diseases

text: Emerging diseases include outbreaks of previously unknown diseases or known diseases whose incidence in humans has significantly increased in the past two decades. Re-emerging diseases are known diseases that have reappeared after a significant decline in incidence (http://www3.niaid.nih.gov/research/topics/emerging).


title: Overview of Retrovirology

text: In the 100 years since their discovery, retroviruses have played a special role in virology and in molecular biology. These agents have been at the center of cancer research and shaped our understanding of cell growth, differentiation and survival in ways that stretch far beyond investigations using these viruses. The discovery of retroviral oncogenes established the central paradigm that altered cellular genes can provide a dominant signal initiating cancer development. Their unique replication mechanism and their integration into cellular DNA allow these viruses to alter the properties of their hosts beyond the life span of the infected individual and contribute to the evolution of species. This same property has made retroviral vectors an important tool for gene therapy. Indeed, the impact of retrovirus research has been far-reaching and despite the amazing progress that has been made, retroviruses continue to reveal new insights into the host – pathogen interaction.


title: Rechtliche Grundlagen und hygienerelevante untergesetzliche Regelwerke

text: Maßnahmen zur Infektionsvermeidung sind immer nur so wirksam, wie sie konsequenterweise angewendet werden. Nicht Gesetze, Verordnungen, Empfehlungen oder Handlungsanweisungen sind dafür das Entscheidende, sondern das ständige Bewusstsein der eigenen Verantwortung als permanenter Begleiter bei jedem Handgriff am Patienten und für den Patienten. Zunehmende Meldungen über Infektionen mit multiresistenten Infektionserregern und über angebliche Hygienemängel in deutschen Kliniken haben die Politik zu Verschärfungen des Infektionsschutzgesetzes bewogen, damit in Medizinischen Einrichtungen eigentlich selbstverständliche (und seit Langem bekannte) Handlungsempfehlungen endlich beachtet und umgesetzt werden. In diesem Kapitel werden die für den Hygienebeauftragten Arzt besonders hygienerelevanten Gesetze und Verordnungen so wie untergesetzliche Regelwerke wie Richt- u. Leitlinien, Empfehlungen zusammengefasst und kommentiert. Hierzu gehören in erster Linie das Infektionsschutzgesetz, die Hygieneverordnungen der Länder, die Empfehlungen von KRINKO und ART sowie die Biostoffverordnung, die TRBA und das Sozialgesetzbuch V.


title: Adjuncts to Resuscitation

text: Damage control resuscitation has been increasingly adopted and practiced over the last decade. The concepts used are not new to this era of medicine but are novel in combination. This chapter will focus on adjuncts to damage control resuscitation (DCR) including massive transfusion protocols, the “other” tenets of damage control resuscitation, hypertonic saline, tranexamic acid, pharmacologic resuscitation, Factor VIIa, and prothrombin complex, and viscoelastic testing.


title: Molecular Techniques for Blood and Blood Product Screening

text: The Food and Drug Administration (FDA) is responsible for ensuring the safety of the more than 15 million units of blood and blood components donated each year in the United States. “Blood banking has become a manufacturing industry, an industry that must conform to high standards and quality control requirements comparable to those of pharmaceutical companies or other regulated industries,” said David A. Kessler, MD, former FDA commissioner [1]. Screening donated blood for infectious diseases that can be transmitted through blood transfusion is a very important step in ensuring safety. The United States has the safest blood supply in the world [1] and the FDA is striving to keep it safe by decreasing the risk of infectious disease transmission. The regulatory agency is continuously updating its requirements and standards for collecting and processing blood. As mentioned earlier, an important step in ensuring safety is the screening of donated blood for infectious diseases. In the United States, tests for infectious diseases are routinely conducted on each unit of donated blood, and these tests are designed to comply with regulatory requirements (Table 28.1). The field of clinical microbiology and virology are now focusing on molecular technology. Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. It is time for all blood safety procedures to include molecular detection techniques. This approach can significantly aid in blood safety to reduce the risk of transmission of serious disease by transfusion. This chapter reviews the current antigen/antibody-based technology, molecular biological technology, and published regulatory policy data for blood safety.


title: Blut und Blutprodukte

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


title: Preventieve gezondheidszorg

text: Het doel van preventie is enerzijds de gezondheid te bevorderen, anderzijds de gezondheid te beschermen. Dit kan bereikt worden door ziekten en aandoeningen te voorkomen of in een vroeg stadium op te sporen en door complicaties te voorkomen. De Wet publieke gezondheid (Wpg) regelt de taken en de bevoegdheden van de overheid op het terrein van infectieziektenbestrijding en collectieve preventie. In het kader van de publieke gezondheidszorg is ook de Wet op het bevolkingsonderzoek (WBO) van belang.


title: Microecology of Infections Associated with Surgery and Trauma

text: Trauma is one of the leading worldwide causes of death at present and fatal trauma cases are the fourth highest cause of death in youths. As a consequence of improved emergency medical treatment, early death rates (48 h post injury) have been significantly reduced. However, death rates resulting from trauma-related complications have not diminished. The most common and dangerous complication that can develop post surgery/trauma is infection caused by opportunistic pathogens, which pose a significant challenge to the healing process ([1]). In addition to interference with the healing process and direct damage to infected tissues caused by the infecting organism, systemic complications, including acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS) and acute renal failure (ARF) can develop. These complications significantly exacerbate a patient’s already deteriorating health and increase recovery times that correlate directly with increased mortality. Therefore, these infections are a major threat to trauma patients, early detection and control of respective infectious agents is essential in decreasing the rates of post trauma-associated morbidity and mortality.


title: Crisis Management in the Twenty-First Century: “Unthinkable” Events in “Inconceivable” Contexts

text: “Unbelievable,” “unthinkable,” “inconceivable”: the twenty-first century opens a new era in the field of risk and crisis management. Many of the major recent crises, including the unconventional 9/11 terrorist attacks; the swift worldwide contamination by the bovine spongiform encephalopathy (BSE, “mad cow disease”), SARS virus, or avian flu; continental blackouts occurring within a few seconds, continent-wide effects of a tsunami in unstable geopolitical zones; and Hurricane Katrina seem to differ fundamentally from the seminal cases that gave birth to disaster research in the 1950s and the 1960s (specific floods, hurricanes, earthquakes) and the crisis management studies in the 1980s (e.g., the Tylenol tampering). The trend seems to be accelerating, so that crises today are increasingly global, intertwined, and “non-textbook” events.


title: Fever in Common Infectious Diseases

text: Infection of the upper airways is very common and is the most common acute illness evaluated in the outpatient setting. The infection is usually caused by viruses including rhinoviruses, influenza viruses, parainfluenza and respiratory syncytial viruses. Influenza is the only viral infection preventable by vaccination and occurs predominately during annual winter epidemics. Bacterial infection such as acute rhinopharyngitis is uncommon and usually presents with either persistent symptoms of an URTI lasting over a week or worsening course after initial improvement or acute onset with high fever and inflammatory changes confined to the pharynx. Fever is common in both bacterial and viral gastroenteritis. High fever is commonly present in many bacterial causes (e.g. Shigella, Salmonella, Shiga toxin-producing E. coli). Fever is often absent or low-grade in other diseases (e.g. enteropathogenic E. coli, cholera). Other febrile conditions cause diarrhoea and need to be differentiated. Fever in CNS infection is the most common presenting symptom in children beyond the neonatal age owing to the presence of inflammatory mediators, particularly IL-1 and TNF in the blood or within the CNS. In MCD, fever was the first symptom in children younger than 5 years and 94% developed fever at some point. Viral exanthems are common causes of febrile illness in children. More than 50 viral agents are known to cause a rash. Historically, exanthems were numbered in the order in which they were differentiated from other exanthems. Thus the first was measles; second, scarlet fever; third, rubella; forth, so-called Filatov-Dukes disease (no longer recognized as an entity); fifth, erythema infectiosum; and sixth, exanthema subitum. As more exanthems were described, numerical assignment became impractical.


title: Animal Models for the Study of Neuroimmunological Disease

text: The development and use of numerous animal models of human autoimmune diseases have provided important advances in our understanding of pathogenic mechanisms of disease and provided robust and reliable models to test novel therapeutic strategies. However, few preclinical studies of therapeutic treatments have demonstrated efficacy in the clinic, possibly because of the biological differences between humans and other animals. Although animal models of human disease are imperfect, it is important to understand the differences between the human disease and its animal models and to design experimental studies using animal models appropriately for the questions being asked. This review provides an overview of the currently used animal models of three human neuroimmunological diseases, multiple sclerosis, Guillain-Barré syndrome, and myasthenia gravis, as well as the advantages and disadvantages of each model and how they correlate or differ from their human counterpart.


title: The Ophthalmic Examination as It Pertains to General Ocular Toxicology: Basic and Advanced Techniques and Species-Associated Findings

text: Ocular toxicology pertains to toxicologic effects of drugs administered topically, intraocularly, or systemically. It should also include evaluation of adverse effects of ophthalmic devices such as contact lenses, intraocular lenses, and glaucoma implants. The ophthalmic examination is able to provide detailed in-life information and is used in combination with clinical observations, clinical pathology, and histopathology to assess potential toxicologic effects. The ophthalmologist must be familiar with the wide range of species used in the field of toxicology, be familiar with the anatomic variations associated with these species, be able to determine what is an inherited or a breed-related finding from a study-related effect, be competent with the required ophthalmic equipment, and be capable of examining this wide range of animals.


title: Control of Foodborne Viruses at Retail

text: Although the number of viruses associated with foodborne outbreaks is relatively small in comparison to their bacterial counterparts, they represent a significant threat to global public health. Moreover, the emergence of novel viruses in food with a greater potential to cause morbidity and mortality suggests that control at the retail level is important. Due to the ability of viruses to persist in the environment and resist many disinfection methods, only a few options are currently viable, yet recent advancements suggest other options may be available in the future. This chapter will provide an overview of the viruses known and postulated to be potential sources of foodborne infection at the retail level, their routes of spread, current regulatory mechanisms in place to prevent infection, as well as explore both proven and new methods for control.


title: Life-threatening Respiratory Failure from H1N1 Influenza: Lessons from the Southern Cone Outbreak

text: A sharp increase in the hospitalization rate for pneumonia, particularly among adults between 20 and 40 years old, and an unusual series of deaths, coincident with an increase in laboratory-confirmed influenza cases, were reported in the spring of 2009 in Mexico. This outbreak appeared after the end of influenza season, and was associated with mortality in a younger age-group than the pattern observed in temperate areas in the northern hemisphere [1]. The concurrent finding of a novel, swine-origin influenza A virus (so called pandemic influenza [H1Nl] 2009) from infected children in the United States [2] completed the picture.


title: Apoptotic Cell Death in Experimental Autoimmune Encephalomyelitis: Apoptosis of effector cells as a safe mechanism in the termination of an autoimmune inflammatory attack

text: Particularly in the vulnerable CNS with a low capacity for regeneration specialized mechanisms must be active for the fast and gentle elimination of dysregulated autoaggressive immune cells. In EAE, local apoptosis of autoimmune T-cells has been identified as a safe means for the removal of these unwanted cells. T-cell apoptosis in situ followed by phagocytic clearance of apoptotic remnants by glia assures a minimum of detrimental bystander damage to the local parenchyma and down-regulates the local inflammatory reaction. The pharmacological augmentation of local apoptosis of inflammatory effector cells might gain therapeutic importance also in human neuroimmunological diseases such as multiple sclerosis.


title: Diagnosis, Discovery and Dissection of Viral Diseases

text: Only a few years ago, viral diagnosis was largely an exercise for academic researchers and public health practitioners with focus on epidemiologic analyses and outbreak prevention, detection, and control. Opportunities for therapeutic intervention were limited to only a few applications such as herpesvirus infections, influenza, and HIV/AIDS; hence, once a bacterial or fungal infection was excluded, clinicians were limited to providing supportive care for what was presumed to be a viral syndrome. Public health organizations tracked the incidence of viral infections and the development of resistance to the few antiviral drugs in use and provided input to governments and the pharmaceutical industry regarding selection of vaccine targets. More recently, interest in viral diagnostics has burgeoned with the advent of new tools for detection and discovery, global recognition of pandemic risk, high-throughput drug screening, rational drug design, and immunotherapeutics. An additional impetus has been the implication of viruses in chronic illnesses not previously attributed to infection. The objective of this chapter is to review the factors responsible for the rise in awareness of viral infections, methods for diagnosis and monitoring viral infections, and future prospects for improvements in discovery, detection, and response to the challenges of clinical virology.


title: Tracing and Preventing Infections

text: A total of 10–20% of somatic patients experience hospital infections during/after hospitalization. Pneumonia, sepsis, surgical site infections and urinary tract infections are most often associated with patient-related use of medical devices for approximately 65% of cases, while nontechnical equipment may be linked to 35% of cases. It is resource-intensive to detect the cause of infection outbreaks and even more expensive not to take action. Unexplained causes of outbreaks may lead to uncertainty and reduced activity at the hospital. To trace and prevent hospital outbreaks, joint efforts from hospital management, microbiology and infection control are needed. This chapter is focused on practical measures to trace and prevent hospital outbreaks.


title: Epidemiology of SFTS in China

text: Severe fever with thrombocytopenia syndrome (SFTS) is a novel emerging virus infection that was first found and reported in Peoples’ Republic of China in 2009 and 2011, respectively. SFTS was later reported in Japan and South Korea, suggesting that SFTS is endemic to East Asian countries. Among these countries, the most SFTS cases have been reported in China. Geographically, SFTS cases have been mainly reported in rural and mountainous areas of the Eastern, Central, and North-Eastern China. So far, the number of SFTS cases has increased and the geographical distribution has expanded in China. From epidemiological studies, it was suggested that various factors including occupation, habit, tick bites, animal contact, environment, meteorological factor, demographic data, clinical symptoms, or laboratory data were associated with SFTS infection or fatal outcome. In this article, epidemiology of SFTS in China is described in detail to assess distributions over time, place, and person.


title: Immunology

text: The concept of forbidden foods that should not be eaten goes back to the Garden of Eden and apart from its religious meanings it may also have foreshadowed the concept of foods that can provoke adverse reactions. Thus we could say that allergic diseases have plagued mankind since the beginning of life on earth. The prophet Job was affected by a condition that following the rare symptoms described by the Holy Bible might be identified as a severe form of atopic dermatitis (AD). The earliest record of an apparently allergic reaction is 2621 B.C., when death from stinging insects was first described by hieroglyphics carved into the walls of the tomb of Pharaoh Menes depicting his death following the sting of a wasp. In 79 A.D., the death of the Roman admiral Pliny the Elder was ascribed to the SO(2)-rich gases emanating from the eruption of Mount Vesuvius. Hippocrates (460–377 B.C.) was probably the first to describe how cow’s milk (CM) could cause gastric upset and hives, proposing dietetic measures including both treatment and prevention for CM allergy.


title: Evaluating Research: Research Designs in Evidence-Based Medicine/Evidence-Based Practice

text: Once you have located some research reports that can help answer your practice question, Step 3 in the evidence-based medicine (EBM) and evidence-based practice (EBP) decision-making model is to appraise the quality and relevance of this research. An initial inspection of materials should help differentiate those that are relevant for your purposes from those that are not. Relevance may often be determined by examining the research question that each study addresses. Studies should have clear and relevant research questions, fitting your practice needs. That is, the topics should fit your clinical question, and the sample should be similar in age and other background criteria. Once these ‘apparently relevant’ studies are identified, the appraisal shifts to issues of research methodology. Even studies that appear be quite relevant initially may later on prove to have important limitations as the details of their methods are explored.


title: Fattori maschili dei disturbi della fertilità

text: In passato sono state tenute conferenze e workshop per stilare delle linee guida sui diversi aspetti dell’andrologia. Questi hanno affrontato, tra l’altro, le seguenti tematiche: l’utilità delle tecniche diagnostiche avanzate di analisi del liquido seminale (ESHRE 1996; Comhaire 1997; Fraser et al. 1997), la gestione dei tumori a cellule germinali testicolari (Krege et al. 2001), la contraccezione delle coppie (Neal e Groat 1976), il ruolo di consulto attento alle coppie infertili (Monach 2003), l’inversione della vasectomia (Chawla et al. 2004) e un’assistenza adeguata (Hull 1996). Allo scopo di limitare la confusione sulla terminologia utilizzata nel campo dell’infertilità (Easton 1998), la WHO ha introdotto alcune definizioni (Rowe et al. 1993).


title: TADs in the Dromedary

text: The transboundary diseases in camel are mainly linked to the regional camel meat market from Sahelian countries (from Mauritania to Somalia) to the Arabian peninsula and North Africa. Indeed, the camel flow in relationship with this market is based on live animals’ export. Because the camel trade can be formal and informal with interconnections between both sectors and despite veterinary controls in the main exporting ports, some diseases such as Rift Valley fever (RVF), PPR-like disease, and MERS-coronavirus can spread from exporting countries to importing ones. However, the epidemiological status of these different diseases is quite variable and the transmission to humans in case of zoonosis (RVF and MERS-Cov) is not necessarily due to transboundary camel trade despite the impact of outbreak on the regional camel market. Globally, dromedary camel is less affected than other ruminants by infectious diseases under transboundary surveillance. But, because camel breeding is concentrated in countries where the disease surveillance systems often lack means, where the frontiers in desert areas are often “porous,” and where the herd mobility is difficult to assess, the risk of transboundary diseases’ transmission through borders is not negligible. Nowadays, the challenge of TADs control is limited to Rift Valley fever, but special attention must be paid to emerging diseases, including the recent discovery of prion disease in Algeria.


title: Innovative Technologies for Advancement of WHO Risk Group 4 Pathogens Research

text: Risk Group 4 pathogens are a group of often lethal human viruses for which there are no widely available vaccines or therapeutics. These viruses are endemic to specific geographic locations and typically cause relatively infrequent, self-limiting, but often devastating human disease outbreaks (e.g. Ebola virus, Kyasanur Forest disease virus, Lassa virus). The overall rarity of disease outbreaks with the associated lack of clinical data and the requirement for research on Risk Group 4 pathogens to be performed in maximum (biosafety level 4) containment necessarily impede progress in medical countermeasure development. Next-generation technologies may aid to bridge the current gaps of knowledge by increasing the amount of useful data that can be gleaned from individual diagnostic samples, possibly even at point-of-care; enable personalized medicine approaches through genomic virus characterization in the clinic; refine our comprehension of pathogenesis by using ex vivo technologies such as organs-on-chips or organoids; identify novel correlates of protection or disease survival that could inform novel medical countermeasure development; or support patient and treatment response monitoring through non-invasive techniques such as medical imaging. This chapter provides an overview of a subset of such technologies and how they may positively impact the field of Risk Group 4 pathogen research in the near future.


title: Sindrome acuta da stress respiratorio (ARDS)

text: L’esatta incidenza dell’ARDS non è nota, poiché nella maggior parte delle diagnosi non viene impiegata una definizione univoca. Si può, comunque, affermare che sussiste una frequenza di circa 2–8 casi di malattia per 100.000 abitanti.


title: Systems Approaches to Map In Vivo RNA–Protein Interactions in Arabidopsis thaliana

text: Proteins that specifically interact with mRNAs orchestrate mRNA processing steps all the way from transcription to decay. Thus, these RNA-binding proteins represent an important control mechanism to double check which proportion of nascent pre-mRNAs is ultimately available for translation into distinct proteins. Here, we discuss recent progress to obtain a systems-level understanding of in vivo RNA–protein interactions in the reference plant Arabidopsis thaliana using protein-centric and RNA-centric methods as well as combined protein binding site and structure probing.


Human monoclonal antibodies for prophylaxis and therapy of viral infections


title: Spatial Structure: Patch Models

text: Discrete spatial heterogenity is introduced into disease transmission models, resulting in large systems of ordinary differential equations. Such metapopulation models describe disease spread on a number of spatial patches. In the first model considered, there is no explicit movement of individuals; rather infectives can pass the disease to susceptibles in other patches. The second type of model explicitly includes rates of travel between patches and also takes account of the resident patch as well as the current patch of individuals. A formula for and useful bounds on the basic reproduction number of the system are determined. Brief descriptions of application of this type of metapopulation model are given to investigate the spread of bovine tuberculosis and the effect of quarantine on the spread of influenza.


title: Shellfish-Associated Viral Disease Outbreaks

text: Numerous outbreaks of shellfish-borne enteric virus illness have been reported worldwide. Most notable among the outbreaks are those involving norovirus illness and hepatitis A. Lessons learned from outbreak investigations indicate that most outbreaks are preventable. Anthropogenic sources of contamination will continue to invade shellfish growing waters, and shellfish, by their very nature, will continue to bioconcentrate these contaminants, including enteric viruses. There is no quick fix for enteric virus contamination of shellfish; however, vigilance on behalf of the industry, regulatory agencies, and the consumer could substantially reduce the incidence of illness. Enhanced monitoring in all areas of shellfish production, harvesting, distribution, and processing would help to reduce viral illnesses. Pollution abatement and improved hygienic practices on behalf of the industry and consumers are needed. New processing and analytical technologies, such as high hydrostatic pressure processing and molecular biological assays, will enhance shellfish safety and continue to provide new avenues to protect the consumer and the industry. Better reporting and epidemiological follow-up of outbreaks are keys to the development of interventions against the foodborne transmission of viral infections.


title: Necrotizing Enterocolitis

text: Necrotizing enterocolitis (NEC) is the most common life threatening surgical and medical emergency affecting the gastrointestinal tract encountered in the neonatal intensive care unit. NEC occurs in 2–5% of all preterm infants although the majority of cases develop in infants less than 36 weeks of gestational age. It has been noted that infants born at earlier gestational age, develop NEC at a later chronological age. The average age of onset of disease is 20.2 days for infants born less than 30 weeks of gestation whereas disease onset is reduced to 13.8 days for infants born at 31–33 weeks and 5.4 days for infants born after 34 weeks of gestation. Epidemiological studies have identifi ed multiple risk factors for NEC, although a history of hypoxia, asphyxia and the introduction of enteral feeding are characteristically associated with premature infants that develop NEC. Despite its predilection for premature infants, NEC has also been described in term infants particularly those with cyanotic heart disease. There is no clear evidence to suggest that geographical origin, ethnicity or gender alter the incidence of NEC.


title: Interstitial Pneumonias

text: The idiopathic interstitial pneumonias are part of the wide spectrum of diffuse parenchymal lung diseases (Fig. 19.1).1 While recognition of diffuse interstitial pulmonary fibrosis can be traced back to studies by Hamman and Rich2 in the 1930s and 1940s, they were first classified as a set of histopathologic patterns in the 1960s by Liebow and Carrington3 into usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), bronchiolitis obliterans with interstitial pneumonia (BIP), giant cell interstitial pneumonia (GIP) and lymphoid interstitial pneumonia (LIP). At about the same time, Scadding4 in the United Kingdom proposed the term fibrosing alveolitis, suggesting (incorrectly) that DIP and UIP were early and late phases of a single disorder.5 There has subsequently been much discussion and controversy over what patterns should be included in such a classification system, in terms of both histology and what these patterns represent regarding clinical disease. As a result, some patterns have now been categorized according to their recognized causes; for example, GIP has been reclassified as a pneumoconiosis, the cause being exposure to cobalt during the production of hard metals or during diamond polishing (see Chapter 26).6,7


Halamine Chemistry and its Applications in Biocidal Textiles and Polymers


title: Healthcare-Associated Infections in Pediatric Hematology-Oncology

text: Pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are at high risk of infections, including healthcare-associated infections (HAIs), resulting in a need to prevent these occurrences when possible. Central line-associated bloodstream infections (CLABSI), Clostridium difficile infection (CDI), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and respiratory viral infections are of particular concern, and the incidence, definition, and other features are reviewed. Currently, standard prevention guidelines exist for selected HAIs, and so the prevention approach for each infection must be considered separately. Prevention strategies have emerged through collaborative efforts, as well as measurement of both process and outcome data. Measurement includes surveillance of infection occurrence; identification and reporting of prevention methods, such as bundles; and the outcomes associated with these approaches. These prevention and measurement approaches are only successful when approached collaboratively with engagement across the entire healthcare team. Through continued measurement and process improvement based on the data collected, more sustainable approaches to infection prevention can be developed. With systematic effort, the occurrence of HAI should be reduced, and patient harm will be prevented.


title: Pandemic Influenza Management and Control Policies: Hospital Coordination During an Influenza Pandemic

text: Since its initial outbreak in April 2009, the pandemic H1N1 virus has posed a challenge to health systems around the world, compelling them to make available the benefits of scientific and medical progress to the entire population. Some of the most significant demands were access to early diagnostics, vaccines, and antiviral treatments as well as the responsiveness of hospital care, particularly in seriously ill patients who required attention in intensive care units (ICUs). The increased demand of medical care during an influenza pandemic is a heavy burden for any health system as it is added to the regular demand for heath care, which should not become paralyzed [1].


title: Social Network Representation and Dissemination of Pre-Exposure Prophylaxis (PrEP): A Semantic Network Analysis of HIV Prevention Drug on Twitter

text: Daily oral pre-exposure prophylaxis (PrEP) is a new approach to HIV prevention. The study aims to examine how PrEP has been represented and disseminated on one of the most popular social networking sites - Twitter. We collected 1435 public tweets containing the word “Truvada.” After computer-mediated and manual de-duplication, we analyzed 447 unique tweets and calculated weights between two words to measure their co-occurrence in 7-word windows. Semantic networks of PrEP-related tweets were constructed. We found that Twitter was used to generate public discussions and collectively interpret new medical information, especially in frequently propagated tweets and from users with more followers. In the meantime, the results revealed the presence of illicit online pharmacies that marketed and sold PrEP without the need for a prescription. We discussed implications for public health and made urgent call for better regulation of online pharmacies.


title: The Molecular Virology of Enteric Viruses

text: Foodborne and waterborne viruses cause a range of illnesses, from acute gastroenteritis (caliciviruses –noroviruses and sapoviruses-, rotaviruses, astroviruses, and enteric adenoviruses), to hepatitis (hepatitis A virus and hepatitis E virus), and other diseases. Recently, next-generation sequencing technologies have allowed the discovery of new enteric viruses (novel astroviruses, kobuviruses, saliviruses, etc.). Noroviruses are the leading cause of acute gastroenteritis outbreaks and sporadic cases in children and adults worldwide and they still remain refractory to routine cell culture propagation. Recent studies have shown that histo-blood group antigens (HBGAs) are cellular carbohydrates that serve as receptors and host susceptibility factors for human noroviruses. They evolve based on antigenic changes and differential glycan binding specificities. In the last years there have been significant advances in the knowledge of their replication mechanisms, pathogenicity and genetic evolution. The strain diversity and the evolution of rotaviruses are also a matter of concern, despite the introduction of rotavirus vaccines. Similarly, molecular analyses of orally transmitted viruses causing hepatitis are clarifying the phylogenetic relationships between these viruses and other viral genera, as well as their pathophysiological mechanisms.


Anthrax-Euronet and Beyond – Challenges of Scientific Research on High Risk Agents


title: Goal-directed Coagulation Management in Major Trauma

text: Severe tissue trauma is frequently associated with hemorrhagic shock and subsequent pronounced coagulopathy [1]. Uncontrolled bleeding is the second most common cause of death, and hemorrhage is directly responsible for 40 % of all trauma-related deaths [2]. Coagulopathy can be detected with standard coagulation tests immediately after arrival in the emergency room (ER) in approximately 25–35 % of all trauma patients [1], [2]. Moreover, early trauma-induced coagulopathy is associated with a 4-fold increase in mortality [1]. Blood coagulation monitoring is essential in order to assess the underlying coagulation disorder and to tailor hemostatic treatment. Thromboelastometry (TEM) and thrombelastography (TEG) are promising point-of-care technologies providing rapid information on the initiation process of clot formation, clot quality, and stability of the clot [3].


title: Depressive Störungen

text: Das Spektrum depressiver Erkrankungen macht den Hauptteil affektiver Störungen aus und gehört mit einer Inzidenz von ca. 8–20% zu den häufigsten psychischen Erkrankungen. Depressionen werden nach wie vor zu selten einer adäquaten Therapie (Antidepressiva, störungsspezifische Psychotherapie wie z. B. kognitive Verhaltenstherapie) zugeführt.


title: Acute Exacerbation of Idiopathic Pulmonary Fibrosis

text: Acute exacerbation of idiopathic pulmonary fibrosis (IPF) is a clinically important complication of IPF that carries a high morbidity and mortality. In the last decade, we have learned much about this event, but there are many remaining questions: What is it? Why does it happen? How can we prevent it? How can we treat it? This chapter attempts to summarize our current understanding of the epidemiology, etiology, and management of acute exacerbation of IPF and point out areas where additional data are sorely needed.


title: PCR Amplification and Sequencing Analysis of Full-Length Turkey Coronavirus Spike Gene

text: Turkey coronaviral enteritis caused by turkey coronavirus (TCoV) continues to infect turkey flocks, resulting in significant economic loss. Determining and understanding genetic relationships among different TCoV isolates or strains is important for controlling the disease. Using two-step RT-PCR assays that amplify the full length of TCoV spike (S) gene, TCoV isolates can be sequenced, analyzed, and genotyped. Described in this chapter is the protocol on PCR amplification and sequencing analysis of full-length TCoV S gene. Such protocol is useful in molecular epidemiology for establishing an effective strategy to control the transmission of TCoV among turkey flocks.


title: Health and Diseases in Africa

text: Compared with other regions of the world; Africa faces more serious health concerns, a heavy burden of diseases and more severely constrained resources for tackling these problems. This state of affairs has been exacerbated by recurring natural disasters, poor economic performance and military conflicts. Under these circumstances, it is not surprising that Africa’s health indicators are worse than those of other parts of the world with serious implications for African development. The chapter argues that despite the recognition of these important health challenges, an understanding of what must be done to improve the health and wellbeing of Africans remains a largely unfinished agenda in today’s development process. This chapter therefore examines the health and disease trajectories with a view to demonstrating and documenting their development implications. It also analyses the various initiatives (regional and global) adopted over time for improved health in Africa, as well as investigating the constraints for achieving health and development in Africa. Actions needed for improved performance are also highlighted.


title: Kawasaki Disease

text: Kawasaki disease, or mucocutaneous lymph node syndrome, was first described in Japan in the late 1960s as an illness characterized by persistent fever, conjunctivitis, mucous membrane changes, acral erythema with desquamation, and cervical adenopathy, associated with coronary arteritis (1,2). While earlier descriptions of the disease were limited to Asia and Hawaii, the disease is now known to occur worldwide. The disease is primarily one of young children, with 85% of cases occurring in children under five years. It is uncommon in children less than 6 months. There have been some epidemiologic investigations linking Kawasaki disease to freshly cleaned carpets, humidifier use, and living near a body of water, but these associations have not been observed consistently (3).


title: Structural Genomics: A Special Emphasis on Membrane Proteins

text: Drug discovery based on structural knowledge has proven useful as several structure-based medicines are already on the market. Structural genomics aims at studying a large number of gene products including whole genomes, topologically similar proteins, protein families and protein subtypes in parallel. Particularly, therapeutically relevant targets have been selected for structural genomics initiatives. In this context, integral membrane proteins, which represent 60–70% of the current drug targets, have been of major interest. Paradoxically, membrane proteins present the last frontier to conquer in structural biology as some 100 high resolution structures among the 30,000 entries in public structural databases are available. The modest success rate on membrane proteins relates to the difficulties in their expression, purification and crystallography. To facilitate technology development large networks providing expertise in molecular biology, protein biochemistry and structural biology have been established. The privately funded MePNet program has studied 100 G protein-coupled receptors, which resulted in high level expression of a large number of receptors at structural biology compatible levels. Currently, selected GPCRs have been purified and subjected to crystallization attempts


title: Inflammation and Inflammatory Diseases, Markers, and Mediators: Role of CRP in Some Inflammatory Diseases

text: The knowledge of inflammation records dates back in first century AD. Initially discovered with features of rubor, tumor, calor, and dolor, scientific investigations have revealed chemical components, cells, and pathways involved in the process of inflammation. The body’s initial defense in response to infection, trauma, or inflammation is through the acute-phase response (APR). APR is a multifaceted set of systemic reactions seen shortly after the experience of a triggering event. One of the many aspects of an APR is the increased hepatic synthesis of positive acute-phase proteins (APPs) leading to increased serum concentration of these proteins. The serum level of these APPs returns to base concentration when the stimulating factor is not anymore present. Today a plethora of inflammatory diseases are causing concern to global health. All the key players and mediators of inflammation change its role with the change in setup of disease and patients. The biomarkers of inflammation and inflammatory mediators are also used as therapeutic targets in under-trial animal models. Even in clinical diagnosis of an inflammatory patient, some broad-spectrum markers were analyzed without individual dissection of each mediator or biomarker. This chapter also provides a review of the acute-phase protein C-reactive protein and its possible use as inflammatory biomarker in diseases. We have highlighted case studies of some patients from Kolkata, India, revealing inflammation from disease together with their clinical history. The question which we probe in here is that whether there is a correlation with the clinical history, C-reactive protein, and inflammation and whether CRP can act as a unique diagnostic and prognostic biomarker in some diseases. The future course of this chapter lies in identifying clinical markers for inflammation, the sequential flow of inflammatory responses for a wide spectrum of diseases and its diagnostic, and therapeutic application to screen out pro-inflammatory diseases vs. anti-inflammatory conditions.


title: Profiling and Searching for RNA Pseudoknot Structures in Genomes

text: A new method is developed that can profile and efficiently search for pseudoknot structures in noncoding RNA genes. It profiles interleaving stems in pseudoknot structures with independent Covariance Model (CM) components. The statistical alignment score for searching is obtained by combining the alignment scores from all CM components. Our experiments show that the model can achieve excellent accuracy on both random and biological data. The efficiency achieved by the method makes it possible to search for the pseudoknot structures in genomes of a variety of organisms.


title: Pulmonary Infection in a Patient After Stem Cell Transplantation

text: A 69-year-old man with a history of hypertension, diabetes mellitus, and acute myelogenous leukemia presented with recurrent fever and cough. He had undergone allogeneic hematopoietic stem cell transplantation from a matched unrelated donor 17 months previously. His posttransplant course was complicated by graft versus host disease and multiple central venous catheter infections with coagulase-negative Staphylococcus spp., vancomycin-resistant Enterococcus, Lactobacillus, and alpha-hemolytic Streptococcus. During his initial course, he also developed a nodular pneumonia, and the subsequent workup included a bronchoscopy that was nondiagnostic.


title: Severe Community-Acquired Pneumonia

text: A 58-years-old male, smoker (8 pack-years) and having Diabetes mellitus and Hypertension for 8 years, presented to the ED with fever and acute dyspnoea for the last 48 h. On examination, respiratory rate was 34 breaths/min, blood pressure-150/96 mm Hg, heart rate-112/min, regular, and Oxygen saturation of 86% on 4L of oxygen by mask. He was conscious and oriented. His chest X-ray showed left lower zone consolidation.


title: Mikrobiologie: Erreger der nosokomialen Pneumonie

text: Das Erregerspektrum der nosokomialen Pneumonie ist breit und unterscheidet sich deutlich von dem der ambulant erworbenen Pneumonie. Im Rahmen der „early onset“ Pneumonie sind S. aureus (MSSA), Haemophilus influenzae und S. pneumoniae führend, während bei der „late onset“ Pneumonie außer den beiden erstgenannten Erregern zusätzlich vor allem eine Reihe von Enterobakterien (am häufigsten E.coli und Klebsiella spp.) sowie Nonfermenter (P. aeruginosa, A. baumannii) gefunden werden. Ein seltener, aber relevanter Erreger ist Aspergillus spp., während Candida spp. keine Erreger sind. Anaerobier spielen eine sehr untergeordnete Rolle; die Bedeutung der Viren ist noch nicht hinreichend geklärt. Legionella spp. können im Rahmen von nosokomialen Ausbrüchen vorkommen. Mikrobiologie, Übertragung, Risikofaktoren, Pathogenese und klinisches Bild werden für die wichtigsten Erreger beschrieben.


Microbiology


title: Lexikalischer Hauptteil

text: a-, an-, gr. Präfixe in Wortzusammensetzungen: 1. als privativum ( α priv.) eine Verneinung od. ein Fehlen, Nichtvorhandensein bezeichnend wie lat. in- od. deutsch un.; vor Konsonanten stets a-, vor Vokalen an-, vor r dagegen als ar- angeglichen; wiedergegeben mit un-, -los od. ohne; 2. als α intensivum eine Verstärkung ausdrückend (kommt seltener vor); 3. als α protheticum mit euphonetischer, rein lautlicher od. wohlklingender Funktion ohne Bedeutungseinfluss, z. B. in astér Stern; 4. a: Analader im Insektenflügel (a(1), a(2) usw.).


title: Spatial Components in Disease Modelling

text: Modelling of infectious diseases could help gain further understanding of their diffusion processes that provide knowledge on the detection of epidemics and decision making for future infection control measures. Conventional disease transmission models are inadequate in considering the diverse nature of a society and its location-specific factors. A new approach incorporating stochastic and spatial factors is necessary to better reflect the situation. However, research on risk factors in disease diffusion is limited in numbers. This paper mapped the different phases of spatial diffusion of SARS in Hong Kong to explore the underlying spatial factors that may have interfered and contributed to the transmission patterns of SARS. Results of the current study provide important bases to inform relevant environmental attributes that could potentially improve the spatial modelling of an infectious disease.


title: Hygiene und Arbeitsschutz

text: Im Rettungsdienst werden unter dem Begriff „Hygiene“ alle vorsorglichen Vorkehrungen und Maßnahmen zusammengefasst, die alle im Krankentransport und Rettungsdienst Tätigen, sowie die zu betreuenden Patienten, vor schädlichen und krankmachenden Einflüssen durch Mikroorganismen schützen sollen.


The Welfare Of Feral Cats


title: Acute and Chronic Right Ventricular Failure

text: Right ventricular failure is the subject of renewed attention as the importance of RV function in a variety of disease states has been recognized. The RV is highly compliant, and is able to accommodate a wide range of preload conditions. Yet, it is afterload-sensitive, and normal physiology is dependent on its association with the low resistance of the pulmonary vasculature. Changes in the pulmonary vascular resistance, either acutely or over time, provoke a series of adaptations that are designed to maintain a normal cardiac output, but ultimately lead to decompensation and RV failure. Through ventricular interdependence, RV failure may impair left ventricular diastolic and systolic function, further reducing cardiac performance. Both echocardiography and magnetic resonance imaging can provide detailed information about RV structure, with MRI providing better assessment of ventricular volumes and RV function. Right heart catheterization is often necessary for definitive diagnosis of the etiology of RV failure and for determining the best therapeutic options. The treatment of RV failure is highly dependent on the underlying etiology, which should be corrected if possible. Targeted medical therapy is particularly useful in cases of pulmonary arterial hypertension, and is under investigation for broader use in other causes of pulmonary hypertension.


title: Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins

text: The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. The structural organisation of both classes of protein is similar with either a single or repeated DNA binding domain preceding a short negatively charged C-terminal tail. In the HMGB class of proteins the HMG DNA-binding domain binds non-specifically and introduces a sharp bend into DNA whereas the AT-hook in the HMGA protein binds preferentially to A/T rich regions of DNA and stabilises a B-DNA structure. The acidic tails are hypothesised to facilitate the interaction of the proteins with nudeosomes by binding to the positively charged histone tails. Both classes of protein also interact with a large number of transcription factors that bind to specific DNA sequences.


title: Pediatric Lung Transplantation

text: Children undergoing lung transplantation present a unique constellation of issues that require compulsive management based upon their underlying diagnosis, state of debilitation, post-transplant needs, and immunosuppression. The ventilator management is also somewhat different from a typically ill child. This chapter will focus on those unique aspects of this group of children with an emphasis on complications seen and the management recommended.


title: Medical Course and Complications After Lung Transplantation

text: Lung transplant prolongs life and improves quality of life in patients with end-stage lung disease. However, survival of lung transplant recipients is shorter compared to patients with other solid organ transplants, due to many unique features of the lung allograft. Patients can develop a multitude of noninfectious (e.g., primary graft dysfunction, pulmonary embolism, rejection, acute and chronic, renal insufficiency, malignancies) and infectious (i.e., bacterial, fungal, and viral) complications and require complex multidisciplinary care. This chapter discusses medical course and complications that patients might experience after lung transplantation.


title: Operation Department: Infection Control

text: Infection control in the operation department is the result of many single factors and routines, based on experience, documentation and expert panels through more than a hundred years. Many factors and routines in surgery are evidence-based, but most of them are still lacking evidence and can probably never be investigated because of ethical problems. Consequently, consensus and guidance are used to a great extent. Surgery opens into sterile tissues for hours, where there is massive tissue damage by knife, diathermy, clogging of vessels, pressure against and drying of tissues, decreased blood supply, impaired phagocytosis and impaired infection defence. Microbes deposited in this devitalized tissues may find a good basis for growth and proliferation if there is lack of infection control and sterility. For patients with ongoing infections and who need surgery, special routines are made to prevent the spread of infections in the operation department. This chapter is a practical description of many important preventive procedures that may protect the surgical patient against surgical site infection (SSI).


title: Global Spread (October 2014)

text: As the Ebola outbreak continued to rage in West Africa, Western countries began to be directly affected by the disease. On the last day of September 2014, the first active Ebola case was diagnosed in the United States. Officials in Dallas, Texas, scrambled to contain the virus. A few weeks later, tension rose dramatically when two of the nurses who treated the initial US patient developed Ebola. One of the nurses traveled to Ohio and back before becoming sick. She flew by plane and had contact with other travelers. Officials were very worried that Ebola flare-ups would start to occur across the country. On October 6, 2014, a nursing assistant in Spain was diagnosed with Ebola. Like the US nurses, she had helped treat a repatriated Ebola victim. On October 23, 2014, a new US case was identified. A doctor was diagnosed with Ebola in New York City after returning from Guinea. On the same day, an Ebola case was discovered in the West African country of Mali. The Ebola outbreak seemed out of control and poised to start a major international epidemic. In West Africa, however, a corner had been turned. Healthcare efforts had shifted from treating all Ebola patients in medical facilities to providing families with supplies to take care of sick patients at home. Toward the end of October 2014, reports started to surface about there being fewer cases in West Africa, especially in Liberia. These reports were initially treated with caution. As time progressed, however, it became clear that the drop in cases was real.


title: Hormone Replacement Therapy: A Critical Review

text: The aim of this chapter is to review the most recent aspects of hormone replacement therapy (HRT), and to clarify its impact on associated health conditions amidst growing uncertainties. Special emphasis has been placed on its effect on cardiovascular conditions and breast cancer, the two most important outcomes affected by HRT, and on identifying ideal candidates for HRT as well as defining the optimum new HRT regimens.


title: Lower Respiratory Tract Infections

text: Lower respiratory tract infections are common and are important in the critical care setting either because they precipitate admission to the critical care unit, e.g. severe viral pneumonia or because they complicate the course of a patient with significant underlying disease or following major surgery, e.g. after multiple trauma. Furthermore, respiratory failure requiring artifical ventialtion is a well recognised reason for critical care support but it can be difficult to determine if this is due to an underlying non-infectious condition such as chronic obstructive pulmonary disease (COPD), infection or a combination of both. The early diagnosis and management of respiratory infection combined with appropriate ventilatory support aids prognosis and the efficient use of critical care facilities given the number of patients affected.


title: Block based semi-global alignment scheme for the analysis of Given DNA sequences

text: Pair wise sequence alignment scheme has been emerged as an efficient computational tool to find region of similarity among sequences of proteins and nucleic acids. As new disease causing viruses are emerging rapidly, new alignment schemes with the advent of fast computers have gained its importance recently. In this paper, we have proposed a block based semi-global alignment scheme to evaluate the optimal alignment between any given two DNA sequences. DNA sequences are divided into blocks of equal length and alignment between the block is determined using dynamic programming. The performances are evaluated in terms of overall matrix score and percentage of similarity. It is inferred from the results, that higher the percentage of similarity between any two blocks, it may code for the same protein/amino acids. The computational complexity of the proposed algorithm is much less compared to that of the general global alignment scheme with O (M, N).


title: Rationale for the Existence of Zoos

text: This chapter looks at the stated goals of zoo mission statements and provides examples of how zoos are addressing their missions. Moreover, with the pressure of zoos to become biological conservation mentors, zoos assume five roles as the executor of the relationship between society and nature. First, zoos take on the role of the “model citizen” by conveying a conservation message. They advocate for a sensible, sustainable use of natural resources and promote less wasteful, green-building alternatives. Many zoological institutions are developing organizational plans that include the use of solar, wind, and thermal power in their daily operations. Additionally, they are growing food for the animals, composting, and using recycled materials in their exhibit design. Second, zoos are maintaining a viable and genetically diverse collection. Zoos are managed under the premise that wildlife conservation is of foremost importance. As zoological institutions have become more active in field studies, their research findings are being applied to larger conservation efforts. Moreover, the conservation research that takes place in situ and ex situ is important in saving small fragmented wild populations. Third, zoos directly influence the attitudes and behaviors of the community in relation to the conservation of plants, animals, and habitats. Due to their urban locations within heavily populated cities, zoos have a unique geographic placement within the community. The urban location of zoos provides them with a unique opportunity to influence government policy. Fourth, the zoo is a conservation mentor. Through mentoring efforts, future generations of scientists and citizens will be more aware of the benefits of long-term conservation. As conservation mentors, zoos must lead the public to become citizen conservationist. Fifth, zoos are a place for people to learn basic facts about organisms and their behavior.


title: Research and application of physical protection technology and equipment against biological contamination in mainland of China

text: Biological contamination is considered to be great hazardous and related to national security, it is very important to strengthen physical protection against biological contamination accordingly. Key technologies of physical protection against biological contamination were described in terms of isolation, positive/negative pressure, air filtration, antibacterial material and disinfection. Present situation of research and development about Chinese physical protection equipment against biological contamination were presented involving individual protection, collective protection, disinfections, quality control and ergonomics. Finally, Chinese and overseas status about physical protection equipment against biological contamination were analyzed and compared in the areas of administration, research and market. It was concluded that Chinese physical protection equipment against biological contamination fell behind in administration, research and industrialization. As a result, some suggestions with Chinese characteristics were presented to promote development of Chinese physical protection equipment against biological contamination.


ACE Inhibition in Heart Failure and Ischaemic Heart Disease


title: Antibiotic Resistance of Non-Pneumococcal Streptococci and Its Clinical Impact

text: Viridans streptococci (VGS) form a phylogenetically heterogeneous group of species belonging to the genus Streptococcus (1). However, they have some common phenotypic properties. They are alfa- or non-haemolytic. They can be differentiated from S. pneumoniae by resistance to optochin and the lack of bile solubility (2). They can be differentiated from the Enterococcus species by their inability to grow in a medium containing 6.5% sodium chloride (2). Earlier, so-called nutritionally variant streptococci were included in the VGS but based on the molecular data they have now been removed to a new genus Abiotrophia (3) and are not included in the discussion below. VGS belong to the normal microbiota of the oral cavities and upper respiratory tracts of humans and animals. They can also be isolated from the female genital tract and all regions of the gastrointestinal tract (2, 3). Several species are included in VGS and are listed elsewhere (2, 3). Clinically the most important species belonging to the VGS are S. mitis, S. sanguis and S. oralis.


title: Pathology of Small Airways

text: The small conducting airways consist of the membranous bronchioles and the respiratory bronchioles. Bronchiolitis is a generic term for inflammatory and fibrotic injuries of these small airways. The histology of normal bronchioles is discussed in detail in Chapter 2. A brief review is warranted here before discussing the histopathologic patterns associated with small airway injury.


Krupp (Pseudokrupp)


Acute Lower Respiratory Infections


title: Central Nervous System Infections

text: Central nervous system (CNS) infections—i.e., infections involving the brain (cerebrum and cerebellum), spinal cord, optic nerves, and their covering membranes—are medical emergencies that are associated with substantial morbidity, mortality, or long-term sequelae that may have catastrophic implications for the quality of life of affected individuals. Acute CNS infections that warrant neurointensive care (ICU) admission fall broadly into three categories—meningitis, encephalitis, and abscesses—and generally result from blood-borne spread of the respective microorganisms. Other causes of CNS infections include head trauma resulting in fractures at the base of the skull or the cribriform plate that can lead to an opening between the CNS and the sinuses, mastoid, the middle ear, or the nasopharynx. Extrinsic contamination of the CNS can occur intraoperatively during neurosurgical procedures. Also, implanted medical devices or adjunct hardware (e.g., shunts, ventriculostomies, or external drainage tubes) and congenital malformations (e.g., spina bifida or sinus tracts) can become colonized and serve as sources or foci of infection. Viruses, such as rabies, herpes simplex virus, or polioviruses, can spread to the CNS via intraneural pathways resulting in encephalitis. If infection occurs at sites (e.g., middle ear or mastoid) contiguous with the CNS, infection may spread directly into the CNS causing brain abscesses; alternatively, the organism may reach the CNS indirectly via venous drainage or the sheaths of cranial and spinal nerves. Abscesses also may become localized in the subdural or epidural spaces. Meningitis results if bacteria spread directly from an abscess to the subarachnoid space. CNS abscesses may be a result of pyogenic meningitis or from septic emboli associated with endocarditis, lung abscess, or other serious purulent infections. Breaches of the blood–brain barrier (BBB) can result in CNS infections. Causes of such breaches include damage (e.g., microhemorrhage or necrosis of surrounding tissue) to the BBB; mechanical obstruction of microvessels by parasitized red blood cells, leukocytes, or platelets; overproduction of cytokines that degrade tight junction proteins; or microbe-specific interactions with the BBB that facilitate transcellular passage of the microorganism. The microorganisms that cause CNS infections include a wide range of bacteria, mycobacteria, yeasts, fungi, viruses, spirochaetes (e.g., neurosyphilis), and parasites (e.g., cerebral malaria and strongyloidiasis). The clinical picture of the various infections can be nonspecific or characterized by distinct, recognizable clinical syndromes. At some juncture, individuals with severe acute CNS infections require critical care management that warrants neuro-ICU admission. The implications for CNS infections are serious and complex and include the increased human and material resources necessary to manage very sick patients, the difficulties in triaging patients with vague or mild symptoms, and ascertaining the precise cause and degree of CNS involvement at the time of admission to the neuro-ICU. This chapter addresses a wide range of severe CNS infections that are better managed in the neuro-ICU. Topics covered include the medical epidemiology of the respective CNS infection; discussions of the relevant neuroanatomy and blood supply (essential for understanding the pathogenesis of CNS infections) and pathophysiology; symptoms and signs; diagnostic procedures, including essential neuroimaging studies; therapeutic options, including empirical therapy where indicated; and the perennial issue of the utility and effectiveness of steroid therapy for certain CNS infections. Finally, therapeutic options and alternatives are discussed, including the choices of antimicrobial agents best able to cross the BBB, supportive therapy, and prognosis.


title: Aerodrome Security

text: The airport is the frontier between the outside world and the State in which the airline passenger lands. It is also the final point at which a person can be checked before embarking on a flight. Moreover, the aerodrome is where cargo is loaded into an aircraft before takeoff. Therefore, security at the airport carries multiple dimensions, from border control to body scanning; from cargo security to security of the aircraft and its passengers.


title: Shiny Framework Based Visualization and Analytics Tool for Middle East Respiratory Syndrome

text: People in the Middle East have been affected by the Middle East Respiratory Syndrome CoronaVirus (MERS Co-V) since 2012. New cases are continuously reported especially in the Kingdom of Saudi Arabia, and the risk of exposure remains an issue. Data visualization plays a vital role in effective analysis of the data. In this paper, we introduce an interactive visualization application for MERS data collected from the Control and Command Centre, Ministry of Health website of Saudi Arabia. The data corresponding to the period from January 1, 2019 to February 28, 2019 was used in the present work. The attributes considered include gender, age, date of reporting, city, region, camel contact, description and status of the patient. The visualization tool has been developed using Shiny framework of R programming language. The application presents information in the form of interactive plots, maps and tables. The salient feature of the tool is that users can view and download data corresponding to the period of their choice. This tool can help decision makers in the detailed analysis of data and hence devise measures to prevent the spread of the disease.


title: The Threat from Viruses

text: Infectious disease represent the most significant threat to human health. Significant geologic cataclysmic events have caused the extinction of countless species, but these “Wrath of God” events predate the emergence of Homo sapiens. Pandemic infections have accompanied the rise of human civilization frequently re-occurring leaving a lasting imprint on human history punctuated by profound loss of life. Emerging infections become endemic and are here to stay marking their presence with an annual death toll. Each decade brings a new onslaught of emerging infectious agents. We are surprised again and again but are never prepared. The long-term consequences often remain unrecognized and are always inconvenient including cancer, cardiovascular disease and immune associated diseases that threaten our health. Reliance on clusters of clinical symptoms in the face of diverse and non-descriptive viral infection symptoms is a foolhardy form of crisis management. Viral success is based on rapid replication resulting in large numbers. Single-stranded RNA viruses with their high replication error rate represent a paradigm for resilience.


title: History and Promise of Plant-Made Vaccines for Animals

text: Plant-made vaccines are now a well-established and well-tested concept in veterinary medicine—yet the only product so far licenced was never produced commercially. This is puzzling, given the breadth of exploration of plant-made animal vaccines, and their immunogenicity and efficacy, over more than twenty years of research. The range of candidate vaccines that have been tested in laboratory animal models includes vaccines for E. coli, Salmonella, Yersinia pestis, foot and mouth disease virus, rabbit haemorrhagic disease virus, rabbit and canine and bovine papillomaviruses, mink enteritis and porcine circovirus, and lately also bluetongue virus, among many others. There are many proofs of efficacy of such vaccines, and regulatory pathways appear to have been explored for their licencing. This review will briefly explore the history of plant-made vaccines for use in animals, and will discuss the unique advantages of plant-made vaccines for use in a veterinary medicine setting in detail, with a proposal of their relevance within the “One Health” paradigm.


title: Studying Vulnerable Populations in the Context of Enhanced Vulnerability

text: The many needs that arise during and immediately following a disaster normally stretch local and national governments and humanitarian organisations to the limit. Both human and financial resources are often inadequate to meet the requirements of medical care, clean water, sufficient food and shelter for victims of the disaster. How, then, can one justify conducting research during or shortly after disaster strikes? People caught in the wake of a disaster are rendered vulnerable by a variety of factors, including injuries, fear, grief, inadequate food and water, loss of housing, and disease outbreaks that sometimes accompany disasters. In addition, an entire population or segments of the population may have been vulnerable to some extent before the disaster struck: they may have food insecurity, lack of potable water, inadequate health care, or be at risk from endemic diseases. Therefore, many people are rendered doubly or even triply vulnerable in the wake of a disaster. The ethical question that arises is whether the vulnerability of victims of a disaster militates against conducting research during or soon after the event.


title: Viral Hepatitis B

text: Hepatitis B virus (HBV) was first discovered on aboriginal Australians in 1963. Epidemiological studies soon recognized that HBV is a global chronic liver disease, with the highest prevalence rates in Asia and Africa. HBV is highly infectious, and in most cases transmitted from family members. Infections acquired during the perinatal period have a 90% chance of progressing to persistent HBV infection. This rate decreases to 2.3% when infection occurs at college student age. The persistent HBV infection starts with the immune tolerance phase when our immune system may recognize HBV antigens, but does not produce significant inflammation. An immune clearance reaction may develop to terminate HBV replication two to four decades later. When this immune clearance reaction successfully suppresses HBV replication, HBsAg carriers may progress to the residual phase. About 50% of HBsAg carriers ultimately clear HBsAg at age 80. Those patients unable to clear HBV replication smoothly have increased risk of chronic hepatitis, liver cirrhosis, and hepatocarcinogenesis. Current therapies decrease hepatic decompensation and increase survival rate. However, the sustained virologic response rate is lower than 40%. About 50% of patients experience a clinical flare within one year after therapy ends. Further studies will be needed to improve sustained virologic response rate.


Bioterrorism Alert for Health Care Workers


title: Pandemic Influenza: Potential Contribution to Disease Burden

text: Records of disease outbreaks resembling influenza date to the writings of Hippocrates (fifth century BPE). Since then, influenza has afflicted humans around the globe. The most severe (“Spanish Flu” 10.1007/978-0-387-78665-0_6287) of three major outbreaks of the twentieth century killed approximately 20–50 million people worldwide. More recently, the global spread of highly pathogenic bird-adapted strain H5N1 is considered a significant pandemic threat. Since 2003, a total of 379 cases and 239 deaths have been reported. This chapter provides an overview of the genetic characteristics of the virus that elucidate its ability to continuously evade a host’s immune system; it describes some of the approaches used to quantify the burden of influenza and discusses their implications for the prevention and containment of future pandemics. The preliminary findings of the studies discussed here suggest that influenza-related burden is highly underestimated in tropical and subtropical regions of the world. This implicates that proper assessment of influenza-related morbidity and mortality worldwide is essential in planning and allocating resources to protect against what could be one of mankind’s most devastating challenges. A summary of learned lessons from past influenza pandemics are described and new intervention strategies aim at curtailing a future pandemic are discussed. More importantly, however, is the discussion of today’s challenges such as antiviral resistance, limited resources in a world that is globally connected and the imminent gap between the capacity (resources available) of developed and developing parts of the world to respond to a pandemic.


China's Pharmaceutical Market: Business Environment and Market Dynamics


title: The Good of Patients and the Good of Society: Striking a Moral Balance

text: The relationship between the good of individual patients and the special good is examined when they are in conflict. The proposition is advanced that the ethical resolution of such conflicts requires an ethic of social medicine comparable to the existing ethic of clinical medicine. Comparing and contrasting the obligations clinicians incur under both aspects of the ethics of medicine is propadeutic to any ordering of priorities between them. The suggested partition of obligations between patient good and the common good is applicable beyond medicine to the other health professions.


title: High-Altitude Pulmonary Edema

text: High-altitude pulmonary edema (HAPE) is an uncommon form of pulmonary edema that occurs in healthy individuals within a few days of arrival at altitudes above 2,500–3,000 m. The crucial pathophysiology is an excessive hypoxia-mediated rise in pulmonary vascular resistance (PVR) or hypoxic pulmonary vasoconstriction (HPV) leading to increased microvascular hydrostatic pressures despite normal left atrial pressure. The resultant hydrostatic stress can cause both dynamic changes in the permeability of the alveolar capillary barrier and mechanical damage leading to leakage of large proteins and erythrocytes into the alveolar space in the absence of inflammation. Bronchoalveolar lavage (BAL) and pulmonary artery (PA) and microvascular pressure measurements in humans confirm that high capillary pressure induces a high-permeability non-inflammatory-type lung edema; a concept termed “capillary stress failure.” Measurements of endothelin and nitric oxide (NO) in exhaled air, NO metabolites in BAL fluid, and NO-dependent endothelial function in the systemic circulation all point to reduced NO availability and increased endothelin in hypoxia as a major cause of the excessive hypoxic PA pressure rise in HAPE-susceptible individuals. Other hypoxia-dependent differences in ventilatory control, sympathetic nervous system activation, endothelial function, and alveolar epithelial sodium and water reabsorption likely contribute additionally to the phenotype of HAPE susceptibility. Recent studies using magnetic resonance imaging in humans strongly suggest nonuniform regional hypoxic arteriolar vasoconstriction as an explanation for how HPV occurring predominantly at the arteriolar level can cause leakage. This compelling but not yet fully proven mechanism predicts that in areas of high blood flow due to lesser vasoconstriction edema will develop owing to pressures that exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance. Numerous strategies aimed at lowering HPV and possibly enhancing active alveolar fluid reabsorption are effective in preventing and treating HAPE. Much has been learned about HAPE in the past four decades such that what was once a mysterious alpine malady is now a well-characterized and preventable lung disease. This chapter will relate the history, pathophysiology, and treatment of HAPE, using it not only to illuminate the condition, but also for the broader lessons it offers in understanding pulmonary vascular regulation and lung fluid balance.