title: Role of Epithelial Cells in Chronic Inflammatory Lung Disease

text: Airborne pathogens entering the lungs first encounter the mucus layer overlaying epithelial cells as a first line of host defense [1, 2]. In addition to serving as the physical barrier to these toxic agents, intact epithelia also are major sources of various macromolecules including antimicrobial agents, antioxidants and antiproteases [3, 4] as well as proinflammatory cytokines and chemokines that initiate and amplify host defensive responses to these toxic agents [5]. Airway epithelial cells can be categorized as either ciliated or secretory [6]. Secretory cells, such as goblet cells and Clara cells, are responsible for the production and secretion of mucus along the apical epithelial surface and, in conjunction with ciliated cells, for the regulation of airway surface liquid viscosity. In addition, submucosal mucus glands connect to the airway lumen through a ciliated duct that propels mucins outward. These glands are present in the larger airways between bands of smooth muscle and cartilage. See Fig. 1.


title: Emerging Disease and the Evolution of Virulence: The Case of the 1918–1919 Influenza Pandemic

text: “Why do parasites harm their host?” is a recurrent question in evolutionary biology and ecology, and has several implications for the biomedical sciences, particularly public health and epidemiology. Contrasting the meaning(s) of the concept of “virulence” in molecular pathology and evolutionary ecology, we review different explanations proposed as to why, and under what conditions, parasites cause harm to their host: whereas the former uses molecular techniques and concepts to explain changes and the nature of virulence seen as a categorical trait, the latter conceptualizes virulence as a phenotypic quantitative trait (usually related to a reduction in the host’s fitness). After describing the biology of emerging influenza viruses we illustrate how the ecological and the molecular approaches provide distinct (but incomplete) explanations of the 1918–19 influenza pandemic. We suggest that an evolutionary approach is necessary to understand the dynamics of disease transmission but that a broader understanding of virulence will ultimately benefit from articulating and integrating the ecological dynamics with cellular mechanisms of virulence. Both ecological and functional perspectives on host-pathogens’ interactions are required to answer the opening question but also to devise appropriate health-care measures in order to prevent (and predict?) future influenza pandemics and other emerging threats. Finally, the difficult co-existence of distinct explanatory frameworks reflects the fact that scientists can work on a same problem using various methodologies but it also highlights the enduring tension between two scientific styles of practice in biomedicine.


title: Emerging Infectious Diseases in Camelids

text: Growing interest in camelids presents a unique challenge to scientists and veterinarians engaged in diagnosing infectious diseases of this species. It is estimated that 65 % of fatalities in Old World camels (OWC, i.e., Camelus dromedarius and C. bactrianus) and 50 % in New World camelids/South American camelids (NWC/SAC, i.e., the domestic alpaca (Vicugna pacos) and llama (Lama glama)) are caused by infectious diseases. Factors that contribute to disease emergence in camelids involve climate change and increased demand for camel products resulting in the intensification of production and expanding camel contacts with other animal species and humans. In this chapter, the most important emerging diseases of camelids are described and discussed. The most notable emerging viral infections in OWC include camelpox, Rift Valley fever (RVF), peste des petits ruminants (PPR), and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Brucellosis, Johne’s disease (JD), and dermatophilosis are the emerging bacterial diseases in OWC. Emerging diseases of NWC include infections with bovine viral diarrhea virus (BVDV), bluetongue (BT), and coronavirus. Parasitic emerging infections in NWCs include the small liver fluke (Dicrocoelium dendriticum) and meningeal worm (Parelaphostrongylus tenuis).


title: An Ensemble Trajectory Method for Real-Time Modeling and Prediction of Unfolding Epidemics: Analysis of the 2005 Marburg Fever Outbreak in Angola

text: We propose a new methodology for the modeling and real time prediction of the course of unfolding epidemic outbreaks. The method posits a class of standard epidemic models and explores uncertainty in empirical data to set up a family of possible outbreak trajectories that span the probability distribution of models parameters and initial conditions. A genetic algorithm is used to estimate likely trajectories consistent with the data and reconstruct the probability distribution of model parameters. In this way the ensemble of trajectories allows for temporal extrapolation to produce estimates of future cases and deaths, with quantified levels of uncertainty. We apply this methodology to an outbreak of Marburg hemorrhagic fever in Angola during 2005 in order to estimate disease epidemiological parameters and assess the effects of interventions. Data for cases and deaths was compiled from World Health Organization as the epidemic unfolded. We describe the outbreak through a standard epidemic model used in the past for Ebola, a closely related viral pathogen. The application of our method allows us to make quantitative prognostics as the outbreak unfolds for the expected time to the end of the epidemic and final numbers of cases and fatalities, which were eventually confirmed. We provided a real time analysis of the effects of intervention and possible under reporting and place bounds on population movements necessary to guarantee that the epidemic did not regain momentum.


title: The Angiotensin-(1-7) Axis: Formation and Metabolism Pathways

text: The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies and pharmacologic blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) is an effective therapeutic regimen. The RAS is now defined as a more complex system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The non-classical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT(7)R pathway that opposes many actions of the Ang II-AT(1)R axis. In lieu of the complexity of this system, the chapter discusses the current evidence on the enzymatic cascade of the Ang-(1-7) axis of the RAS regarding the peptidases that contribute to the formation and degradation of the peptide in the circulation and various tissues.


title: Infectious Diseases and the Kidney

text: The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function.


title: Genetic Diversity of Microbial Endophytes and Their Biotechnical Applications

text: The need for new and useful compounds and biological processes to provide assistance and relief in all aspects of the human condition is ever growing. Drug resistance in bacteria, the appearance of life-threatening viruses, and a tremendous increase in the incidence of fungal and drug-resistant bacterial infections in the world’s population, each only underscores our inadequacy to cope with these medical problems. Added to this are enormous difficulties in raising enough food on certain areas of the earth to support local human populations. Environmental degradation, loss of biodiversity, and spoilage of land and water also add to problems facing mankind. In addition, there is the need for bio-derived fuels to supplant the ever-growing demand for petroleum and petroleum products.


title: Tracheobronchitis und Bronchiolitis

text: Definition. Bronchitis im Kindesalter ist eine durch Infektionserreger ausgelöste entzündliche Krankheit der Bronchien, bei der durch den gleichen Erreger häufig auch weitere Teile der Luftwege mitbefallen sind. Die chronische Bronchitis ist im Kindesalter nicht definiert und kommt entsprechend der Definition für Erwachsene (3 oder mehr Monate mit produktivem Husten über 2 oder mehrere aufeinanderfolgende Jahre) nicht vor. Kinder mit häufigen Bronchitiden (mehr als 6 pro Jahr) werden jedoch häufig gesehen.


title: Governance of Food Security in the 21(st) Century

text: Governance is broadly defined as the exercise of power in an institutional context with the main aim of directing, controlling, and regulating activities concerned with the public interest.


title: Aspiration, Bronchial Obstruction, Bronchiectasis, and Related Disorders

text: The conducting airways play a pivotal role in the spectrum of pulmonary pathology, not only as conduits for injurious agents to enter the lung, but also as an anatomic compartment that is affected by a diverse array of primary or secondary bronchocentric diseases. This chapter discusses aspiration and bronchial obstruction in detail, with emphasis on the aspiration of toxic, infective, or particulate matter. Lung abscess, a frequent complication of obstruction or aspiration, is also reviewed. Both aspiration and lung abscess are reconsidered within the context of pulmonary infectious disease mainly in Chapter 8 on bacterial infections, and to some extent in the chapters on mycobacterial (Chapter 9), fungal (Chapter 10), and parasitic diseases (Chapter 14).


title: The Sixth Mass Extinction

text: After the five mass extinctions on Earth that were caused by meteorite impacts, volcanism and large-scale climate change, several scientists predict that we are currently at the beginning of a sixth mass extinction. In this scenario, it is humankind that is causing the mass extinction with the illegal trade in wildlife as one of the most important hazards to wildlife species. This chapter presents an analysis of the causes and consequences of the global defaunation in the context of technological innovation and industrialisation of the wildlife trade. The complexity of the current decline of biodiversity and the effect of defaunation will be demonstrated by the sensibility of ecological interaction between animals and plants. The exploitation of natural resources has become a part of the social, political and economic dynamics.


title: Farming human pathogens

text: Here we examine examples of the farming of coevolutionary systems, focusing on the mutually amplifying roles of large-scale psychosocial stress, economic structure, and reductionist interventions in the ecology and evolution of highly adaptive disease organisms. We find, in general, that population-level socioeconomic and other stressors, in synergism with reductionist interventions, are precisely suited to trigger mesoscale resonance coevolutionary resilience domain shifts affecting rapidly evolving pathogens.


title: Pre-primary and Primary Prophylaxis of Variceal Hemorrhage

text: Variceal hemorrhage is a life-threatening complication of portal hypertension. Thus, prevention of variceal formation (pre-primary prophylaxis) or at least prevention of variceal bleeding are important goals to improve life quality and—if possible—survival of patients with liver cirrhosis. Interruption of the underlying cause of liver disease is the most successful approach, which, however, often fails. For this situation interruption or modulation of different pathophysiological mechanisms leading to fibrosis, hyperdynamic circulation and portal hypertension have been shown effective in animal models. But few could be translated to humans. By contrast, different steps to prevent first bleeding from varices have proven successful in many clinical trials. These applied mainly drugs to lower portal pressure, such as nonselective β-blockers, or endoscopic obliteration of varices, while prophylactic shunt procedures are not advised.


title: Cardiovascular Emergencies

text: A good focused history is essential to the adequate assessment of chest pain. It is important to rapidly exclude potentially life-threatening causes of chest pain to avoid adverse clinical outcomes.This should be preceded by an ABCD (airway, breathing, circulation, disability) assessment. Once cardiac chest pain is determined to be likely, early risk stratification should be achieved in order to guide choice of further management.


title: Common Infections Following Lung Transplantation

text: The lungs are the only transplanted organ in direct contact with the ‘outside world’. Infection is a significant cause of morbidity and mortality in lung transplantation. Early accurate diagnosis and optimal management is essential to prevent short and long term complications. Bacteria, including Mycobacteria and Nocardia, viruses and fungi are common pathogens. Organisms may be present in the recipient prior to transplantation, transmitted with the donor lungs or acquired after transplantation. The degree of immunosuppression and the routine use of antimicrobial prophylaxis alters the pattern of post-transplant infections.


title: An RT-PCR Assay for Detection of Infectious Bronchitis Coronavirus Serotypes

text: Avian infectious bronchitis virus (IBV), a chicken Gammacoronavirus, is a major poultry pathogen, and is probably endemic in all regions with intensive poultry production. Since IBV was first described in 1936, many serotypes and variants of IBV have been isolated worldwide. IBV isolates are capable of infecting a large range of epithelial surfaces of the chicken, involving the respiratory, renal, and reproductive systems; however, the clinical signs are usually not specific for differential diagnoses. Virus isolation is commonly used for diagnosis of IBV infection, which was achieved through passage of clinical materials via the allantoic route of embryos. Currently, more sensitive molecular approaches for the detection of avian pathogens have been developed, including reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR, which are more suitable for use in diagnostic laboratories. In this chapter, we describe a one-step RT-PCR which can be used for detecting most of IBV serotypes in the IBV-infected allantoic fluid and has been used routinely in our laboratories for detection of IBVs.


Human and Animal Viruses in Food (Including Taxonomy of Enteric Viruses)


The welfare of laboratory rabbits


title: The US CDC Global AIDS Program in China

text: The China-US Cooperation-Global AIDS Program (GAP) was a strategic technical collaboration program jointly implemented by the US Centers for Disease Control and Prevention and the Chinese Center for Disease Control and Prevention. This program developed, piloted, launched, and evaluated a broad range of projects supporting national and local HIV prevention and control programs; evidence-based decision-making; strengthening systems and capacity at national, provincial, and local levels; prioritizing high-risk geographic areas and populations; developing innovative approaches for scale-up; answering important scientific questions that can be most effectively answered in China but also with global implications for the HIV response; and increasing China’s engagement with the global public health community and sharing critical lessons learned. A productive working relationship with well-conceived models, a results-based activity implementation plan, and proper linkage to the domestic policy process has made a significant contribution to HIV control and prevention in China.


title: State Capacity and Leadership in ASEAN and the EU

text: This chapter examines state capacity as an explanatory factor in order to reconceptualise political leadership in a regional context. This chapter argues that state capacity is crucial in the provision of political leadership in a regional context as it helps to sustain the benefits of regional community-building, and to continually, over time, build and strengthen regional community-building through policy implementation and policy continuation. This chapter compares the role, and the implications of, the Franco-German alliance in steering the development of the EU, with the more circumspect role of Indonesia as the de facto leader in ASEAN, whether in providing sole leadership, or through a coalition with other countries. It also examines and compares both the potential and challenges for smaller member states such as Singapore in ASEAN and the Benelux countries in the EU, to exert increased influence in their regional community-building efforts.


title: Bioterrorism

text: This final section examines a mode of attack which has been repeatedly connected with nuclear terrorism in the debate over security. The weapons, usually phials or bottles, are so small that they easily avoid detection and with this kind of attack there is of course no moment of detonation, only a gradual increase in casualties. And the human carriers can themselves function as human weapons. This fiction repeatedly plays on different meanings to “cell”, relating the fate of individuals to that of the body politic. Once again the conspirators might be Middle Eastern or domestic, the latter frequently lone wolves as happens in Richard Preston’s The Cobra Event, which reportedly shaped the policy of the Clinton administration.


title: Complications and Toxicities Associated with Cancer Therapies in the Intensive Care Unit

text: Advances in the management of hematologic malignancies and solid tumors have given rise to diverse modalities to treat cancer other than cytotoxic chemotherapy, including targeted therapies, immunotherapies, and cellular therapies. Currently, there are over 175 FDA-approved antineoplastic agents in the United States, many with a diverse and profound toxicity profile. Complications of antineoplastic therapy may result in the need for intensive care unit (ICU) admission to provide acute symptom management. Accordingly, ICU providers caring for cancer patients should have a working knowledge of the toxicities and complications associated with antineoplastic therapy.


title: Obliterative Bronchiolitis

text: Obliterative bronchiolitis (OB) is a condition characterized by inflammation and fibrosis of the bronchiolar walls resulting in narrowing or obliteration of the bronchiolar lumen. The most common causes are childhood lower respiratory tract infection, hematopoietic stem cell or lung and heart-lung transplantation, and toxic fume inhalation. The most frequent clinical manifestations are progressive dyspnea and dry cough. Pulmonary function tests demonstrate airflow obstruction and air trapping. Radiographic manifestations include reduction of the peripheral vascular markings, increased lung lucency, and overinflation. The chest radiograph, however, is often normal. High-resolution CT is currently the imaging modality of choice in the assessment of patients with suspected or proven OB. The characteristic findings on high-resolution CT consist of areas of decreased attenuation and vascularity (mosaic perfusion pattern) on inspiratory scans and air trapping on expiratory scans. Other CT findings of OB include bronchiectasis and bronchiolectasis, bronchial wall thickening, small centrilobular nodules, and three-in-bud opacities. Recent studies suggest that hyperpolarized (3)He-enhanced magnetic resonance imaging may allow earlier recognition of obstructive airway disease and therefore may be useful in the diagnosis and follow-up of patients with OB.


title: Infections in Heart, Lung, and Heart-Lung Transplantation

text: Half a century has passed since the first orthotopic heart transplant took place. Surgical innovations allowed for heart, lung, and heart-lung transplantation to save lives of patients with incurable chronic cardiopulmonary conditions. The complexity of the surgical interventions, chronic host health conditions, and antirejection immunosuppressive medications makes infectious complications common. Infections have remained one of the main barriers for successful transplantation and a source of significant morbidity and mortality. Recognition of infections and its management in this setting require outstanding clinical skills since transplant recipients may not exhibit classic signs or symptoms of disease, and laboratory work has some pitfalls. The prevention, identification, and management of infectious diseases complications in this population are a priority to undertake to improve the medical outcomes of transplantation. Herein, we reviewed the historical aspects, epidemiology, and prophylaxis of infections in heart, lung, and heart-lung transplantation. We also discuss the most prevalent organisms affecting the host and the organ systems involved.


title: Basics of Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

text: In this chapter, the basic principles of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) (Sects. 2.2, 2.3, and 2.4), the technical components of the MRI scanner (Sect. 2.5), and the basics of contrast agents and the application thereof (Sect. 2.6) are described. Furthermore, flow phenomena and MR angiography (Sect. 2.7) as well as diffusion and tensor imaging (Sect. 2.7) are elucidated.


title: Environmental Determinants of Health

text: Several modifiable environmental factors—such as outdoor air pollution, household air pollution, drinking water contamination, occupational exposure to hazardous materials, lead exposure, and built environments that discourage physical activity—influence the risk and experience of chronic disease. The World Health Organization estimates that 21.2% of global deaths and 16.3% of global disability-adjusted life years lost are attributable to these risk factors. There are several approaches for estimating the number of deaths and chronic illnesses attributable to these factors. Managing and mitigating environmentally related chronic illness begins with the administration of an environmental health history.


Entwicklung von Arzneistoffen


title: Boyhood

text: In those years, even in the most intellectual families, it was not customary and actually considered counterproductive to teach children to read before starting school (“the child would be bored in class”). But my mother was sure that her “treasure” devouring one thick volume after another would be a straight “A” student and infected me with this confidence too. Alas, the first days at school turned out to be a real shock to me. The fact that I could read fluently did not help me at all. Having just one time relished my virtuosic ability to read, the teacher Nina Vasilyevna Smirnova did not call on me any more, concentrating on teaching the overwhelming majority “Russian oral skills”. There were exactly 40 students in the class.


title: Improving the Human Well-Being of All Africans

text: Integrated organic growth must prioritise the interests of the African people by creating equal economic opportunities, generating social and cultural wealth and capital, to a broad spectrum of the population in each country. Human development seeks to enable people to lead full, productive and meaningful lives by raising their incomes and improving their standards of living, which include life expectancy, health, education, security and personal liberty and freedom of choice—unfortunately, Africa fares poorly in this regard if one considers the Human Development Index or the World Happiness Report. China is particularly active in interventions in Africa that aim to improve food security, social development, medical care and public health, poverty eradication, education, environmental protection, security, immigration, law enforcement and international cooperation. One example is China’s significant intervention during the Ebola outbreak crisis in West Africa which saved countless lives. Concerns do, however, remain regarding possible human rights abuses and lack of community engagement by Chinese investors in Africa.


title: A Woman with a History of a 2-Year Stay in Gabon and Onset of a Cyclical Fever More Than 1 Year Later

text: A 23-year-old woman with no significant past medical history presented with fever every other day for 1 week. After graduating from college, she had spent a year as in Gabon, West Africa, before starting medical school. She was healthy until 1 week prior to presentation. At that time, she developed fever up to 102.5 °F, as well as chills and sweats, with symptoms occurring every other day. She also noted myalgia, headache, profuse sweats with defervescence of the fever, and intense fatigue.


title: Epidemiology of Respiratory Allergies and Asthma

text: Asthma has puzzled and confused physicians from the time of Hippocrates to the present day. The word “asthma” comes from a Greek word meaning “panting” (Keeney 1964), but reference to asthma can also be found in ancient Egyptian, Hebrew, and Indian medical writings (Ellul-Micallef 1976; Unger and Harris 1974). There were clear observations of patients experiencing attacks of asthma in the second century and evidence of disordered anatomy in the lung as far back as the seventeenth century (Dring et al. 1689).


title: HIV/AIDS: Lessons from a New Disease Pandemic

text: The acquired immunodeficiency syndrome (AIDS) was first recognized about 25 years ago (Gottlieb et al., 1981; Masur et al., 1981; Siegal et al., 1981). The best available evidence suggests that HIV newly infected the human species about 50–100 years ago (Korber et al., 2000). It did not originate in Asia. It apparently moved to people from sub-human primates in Africa (Keele et al., 2006; Kanki, 1997). Because of different clinical presentations in different populations of people, and a long incubation period, it was more difficult to diagnose than SARS or avian influenza. As a new epidemic that originated in the era of modern medicine, it taught us many lessons about the difficulties that a new infectious disease can present. Already claiming at least 60–80 million victims, AIDS seems destined to continue as a pandemic for the foreseeable future. Drugs that control HIV replication and reverse disease progression have been developed, but none eliminate the virus from the body. Sexual transmission can be prevented by abstinence or condoms, but such measures, which prevent procreation, provide only limited value. Approaches for making a vaccine using conventional techniques have failed. Most experts believe that an effective vaccine will be made eventually, but not for at least 10–20 years. We need to learn more about the immunobiology of acute HIV infection, and about potentially protective immunoepitopes, such as conformational intermediates of the virus envelope. Until a vaccine is available, there is little or no chance that HIV can be eliminated, or even drastically reduced in prevalence. AIDS has presented scientists, political leaders, and health policy experts with unprecedented challenges.


title: Uncoordinated Human Responses During Epidemic Outbreaks

text: Uncoordinated human behavioral responses triggered by risk perception can alter the evolution of an epidemic outbreak further and beyond control measures imposed by public authorities. In fact, spontaneous behavioral changes could develop as a defensive response during the spread of an epidemic, thereby impacting the epidemic dynamics and affecting timing and overall number of cases. In this chapter, a model coupling the classic SIR disease transmission model with an imitation dynamics process is introduced which accounts for the diffusion of different behaviors in the population as a response to the epidemic threat. A detailed analysis of the model identifies the main determinants leading to remarkable alterations in infection dynamics in both risk perception and diffusion of human behavioral patterns. Empirical evidence points to the need of incorporating human behavior in prediction models informing public health decisions.


title: Skin Infections

text: Cutaneous infections are common in immunocompromised patients. Neutropenia predisposes patients to fungal, bacterial and viral infections. Antibacterial antifungal and antiviral prophylaxis have caused a significant reduction in some of these infections. There are two main types of cutaneous infections : primary cutaneous infections and cutaneous manifestations of a disseminated infection. In the latter, skin lesions may be the window to disseminated bloodstream infection and the first and only evidence of a disseminated life threatening infection. The diagnosis may be at your fingertips; therefore a thorough skin exam is the clue. However, it’s also important to know the characteristic lesions associated with different infections. It will help expedite diagnosis so appropriate treatment is initiated promptly in neutropenic patients, which can be lifesaving. In a retrospective study of 43 neutropenic febrile patients with cutaneous lesions, fungal infections were the most frequent, and nodular lesions on the lower extremities were the most prevalent (Naorungroj and Aiempanakit, J Am Acad Dermatol 74:AB166, 2016). Skin biopsy for pathological study and culture remains the gold standard and should be obtained early to confirm the suspected diagnosis. In these immunocompromised patients the inflammatory response is altered by either the primary disease or its treatment. Therefore, routine pathogens may present in an atypical fashion, with diminished or absent induration, erythema, or pustulation in response to bacterial resulting cutaneous infection without typical cellulitis (Urabe, Clin Infect Dis 39:S53–S55, 2004). Skin lesions are evaluated not only by morphology, but also in the context of the clinical setting and biopsy result. The skin biopsy is inexpensive, relatively noninvasive and without contraindication, and may avoid the need for more invasive procedures such an open lung biopsy (Grossman, et al., Cutaneous manifestations of infection in the immunocompromised host. Springer Science+Business Media, LLC, New York, 2012). In addition to antimicrobial therapy, surgery should not be postponed in the face of progressive skin and soft tissue infection in this population (Brzozowski and Ross, J Hand Surg Br 22:679–680, 1997).


title: Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry

text: The combination of a fluorine atom and a diazine ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated biologically active agents. Herein we give a comprehensive review on the biological activity and synthesis of fluorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry.


title: HIV: Biology to Treatment

text: AIDS is one of the most dreaded diseases of the twenty-first century caused by human immunodeficiency virus (HIV). Recently, there are reports which show decline in new infections due to better access to anti-retroviral drugs. Still on a daily basis, ~2356 new HIV infections are being reported globally. New treatments and anti-HIV drugs are being continuously developed with the aim to control and cure AIDS. The anti-HIV drugs that are in use usually target HIV entry and replication inside the host cells. However, these drugs are only partially effective in slowing the rate of HIV replication. Nevertheless, the virus manages to replicate at much slower rates even when anti-retroviral treatment is ongoing. The HIV seropositives who are on anti-retroviral treatment for long periods of time are now developing different kinds of other complications including neuroAIDS. The latest development in HIV therapy is a novel kind of bone marrow transplantation from donors who have a homozygous mutation in CCR5 gene.


title: Leidraad algemene diagnostiek/therapie bij cardiale ziektebeelden

text: Bijzondere vorm van cardiomyopathie met vervanging van normaal rechterventrikelmyocard door vet en fibrotisch weefsel.


title: Airspace-Occupying Diseases

text: Diseases of the air space of the lung share many common findings and presentation that it makes more sense to be grouped together in a differential diagnosis. The common imaging finding is usually as a lung infiltrate or consolidation of some type of distribution or another. Trying to find the putative cause for the imaging pattern is a good first step in narrowing the differential diagnosis and answering the question: what accounts for this pattern on imaging studies? Most of these diseases have an acute or subacute onset and exhibit restrictive pattern on pulmonary function tests. When treated promptly, they resolve completely with little or no residual injury to the lung architecture. On a small biopsy it is important to have a clinical history and imaging results before embarking on a descriptive rather than a definitive diagnosis. The smaller the sample, the more information is needed to complete the picture. Pulmonologists should be advised to target the part of the lung that should provide the most information related to the process under investigation. An endobronchial wall biopsy is not suitable in the setting of investigating a lung infiltrate as part of the alveolated lung has to be included. The category of airspace-occupying diseases of the lung includes: 1. Acute lung infections such as bacterial and viral pneumonias. 2. Acute lung injury pattern which includes bronchiolitis obliterans/organizing pneumonia and diffuse alveolar damage. 3. Intra-alveolar hemorrhage. 4. Pulmonary alveolar proteinosis. 5. Pulmonary edema. 6. Pneumocystis pneumonia. 7. Lymphangitic carcinomatosis. In all of these instances, there are ground-glass opacities obscuring the air space. Most clinicians would describe the imaging as “infiltrate” or “consolidation.” The task for the pathologist is to find the pertinent finding that could account for the imaging.


title: How Masqueraders Infiltrate a System

text: The U.S. and China take cyber surveillance very seriously. Therefore, let the U.S. get on with it. Finally, that’s the only way of becoming a superpower.


title: Concepts of Security Threats, Challenges, Vulnerabilities and Risks

text: The reconceptualization of security has been triggered by the end of the Cold War, by the process of globalization, and by the gradual transition from the Holocene to the Anthropocene phase of earth history (Brauch 2008, 2009, chap. 1 by Brauch/Oswald Spring above). From a philosophical perspective, in the contemporary security discussion the “dual moment of prevention and compensation of genuinely social and technical uncertainties” (Makropoulos 1995: 745–750) becomes decisive.


title: Acronyms and Abbreviations

text: n many fields today abbreviations and acronyms are common. They provide a useful tool for shortening long words or expression in order to save time and space. Some well-known general examples are DVD (digital versatile disc), UNICEF (United Nations International Children’s Emergency Fund), NASA (National Aeronautics and Space Administration), and UN (United Nations). Abbreviations are extensively used in the scientific and medical communities. It is common practice to use abbreviations for long names of many clinical diseases and procedures, and for scientific techniques that have to be repeated many times in medical or scientific papers, posters, and oral presentations. This can cause substantial communication difficulties for individuals who are not familiar with English abbreviations in their field. The example below is meaningless to individuals who are not familiar with the abbreviations used.


title: Poverty, Health and Livelihoods

text: Developing countries, especially those in the tropical regions of the world, are known for poverty and infectious diseases (ID). People in developing countries carry on their day-to-day living amongst these two challenges. Between the years 1940–2004, over 300 emerging human ID have been reported worldwide. Infectious diseases have resulted in high mortality and morbidity in developing countries. Affecting more than 1 billion of the world’s population, neglected tropical diseases (NTD) are a group of infectious diseases that are endemic in the poorest regions of the world. Most of the affected populations live in rural areas with very minimal resources but at high risk of disease due to their livelihood. Non-communicable diseases are also on the increase in developing countries, further exacerbating public health challenges in these regions. With nearly 15 million people dying each year as a result of ID, most of them living in developing countries, there is need to find solutions to prevent and tackle infectious diseases in these communities. This book is devoted to infectious diseases and livelihoods in developing countries.


Epitopes are defined as the molecular structures interacting with specific receptors of the immune system such as antibodies, MHC, and T cell receptor molecules. The Immune Epitope Database and Analysis Resource (IEDB, http://www.immuneepitope.org) is a database specifically devoted to immune epitope data. The database is populated with intrinsic and context-dependent epitope data curated from the scientific literature by immunologists, biochemists, and microbiologists. An analysis resource is linked to the database which hosts various bioinformatics tools to analyze epitope data as well as to predict de novo epitopes. The availability of the IEDB will facilitate the exploration of immunity to infectious diseases, allergies, autoimmune diseases, and cancer. The utility of the IEDB was recently demonstrated through a comprehensive analysis of all current information regarding antibody and T cell epitopes derived from influenza A and determining possible cross-reactivity among H5N1 avian flu and human flu viruses.


title: Diplomacy and Global Health Security

text: This chapter discusses the concept of global health security, the key challenges it raises and the role of diplomacy in addressing them. It begins by outlining an expanded understanding of security, describing the concept of health security, including the dual aspects of societal health security and individual, or personal, health security. The political context is also described. Key issues in societal health security are then outlined, including significant threats and current responses. Threats covered include the emergence of infectious diseases that cross the species barrier from animals to humans, climate change, the deliberate use of disease-causing agents and the growing burden of non-communicable diseases. Current approaches to addressing threats to societal health security are discussed, along with the role to be played by international affairs. The chapter then describes key issues in individual health security, including reliable access to medicines and other health-related products and services; and the politically and economically sensitive determinants of access. The chapter then discusses how to ensure stronger global health security in the future.


title: Airborne Precautions and Personal Protective Equipment: The Powered Air-Purifying Respirator-Only Approach

text: Airborne isolation of patients and use of respirators are a foundational strategy to prevent transmission of pathogens like tuberculosis and novel respiratory viruses via airborne route in healthcare settings. Healthcare personnel respiratory protection programs utilize respirators, which may or may not require fit testing for each individual. This chapter reviews the different types of respirators, which include the more common N95 respirator masks and the somewhat less commonly used powered air-purifying respirators, and the levels of protection offered by each type. The chapter also reviews considerations and controversies regarding use of N95 respirators and PAPRs and situations when a PAPR-only approach might work. In each healthcare facility, the epidemiology and risk assessment of the facility, available evidence in published literature, and certain regulatory standards must inform the clinical policies, protocols, and procedures. Key unanswered questions and further areas for research are outlined.


title: Origins

text: When the first warm breezes of April blow in from Buzzard’s Bay, the South End of New Bedford, near the elbow of the Massachusetts coast as it extends eastward out to Cape Cod, changes character entirely. Not that the fast-food places, convenience stores, double-decker tenements, or boarded-up businesses transform magically into some sort of suburban Valhalla, but the change of season at least encourages people to go out on the streets and makes everything seem a little brighter.


Constructal Pattern Formation in Nature, Pedestrian Motion, and Epidemics Propagation


title: Varieties of Corporate Social Responsibility

text: This chapter distinguishes among several versions of capitalism that have very different views of corporate social responsibility (CSR): the maximization of $ value shareholder, the balance the interests of stakeholders view, and the sustainability model that is the official position of the European Union (EU). The Chapter then considers CSR in Japan, and in countries like India and China that have a system of “state capitalism.” I argue that the view of corporate social responsibility (CSR) held by the EU sustainability model of corporate social responsibility is morally superior. I also contend that the American finance based model of philanthropic CSR is not economically adequate in the new international economic order.


title: Viral Upper Respiratory Tract Infections

text: The upper respiratory system is one of the most common sites of infection for adults, but even more so for children. Several viruses, from variable families, cause upper respiratory infections which, although generally underestimated due to their typically self-limiting nature, underlie enormous healthcare resource utilization and financial burden. Such, otherwise “benign” infections, can have very significant sequelae both in the form of bringing about local complications but also inducing asthma attacks, thus greatly increasing morbidity. Their enormous prevalence also indicates that rigorous research should be undertaken in order to tackle them, in both the prevention and treatment field.


title: Prevention of Infections in Patients with Hematological Malignancies

text: Infection is a frequent complication and a leading cause of morbidity and mortality in patients with hematological malignancies. Problems associated with the management of infections in these patients include difficulties in early diagnosis because the clinical signs of infection are subtle, the low performance of diagnostic tests, and suboptimal response to treatment because recovery of host defenses is a key factor for resolution of infection. Preventing these infections relies on infection control measures and antimicrobial chemoprophylaxis. While infection control measures are safe (but not always effective), the use of antimicrobial agents for prophylaxis of infection is not devoid of problems. Its wide use may increase the possibility of the development of resistance, select for resistant organisms, and increase toxicity and cost. Therefore, any attempt to administer an antimicrobial agent should be accompanied by a reflection of the potential benefits and risks of prophylaxis.


title: Memetic Algorithms with Partial Lamarckism for the Shortest Common Supersequence Problem

text: The Shortest Common Supersequence problem is a hard combinatorial optimization problem with numerous practical applications. We consider the use of memetic algorithms (MAs) for solving this problem. A specialized local-improvement operator based on character removal and heuristic repairing plays a central role in the MA. The tradeoff between the improvement achieved by this operator and its computational cost is analyzed. Empirical results indicate that strategies based on partial lamarckism (i.e., moderate use of the improvement operator) are slightly superior to full-lamarckism and no-lamarckism.


title: MARs and MARBPs: Key modulators of gene regulation and disease manifestation

text: The DNA in eukaryotic genome is compartmentalized into various domains by a series of loops tethered onto the base of nuclear matrix. Scaffold/ Matrix attachment regions (S/MAR) punctuate these attachment sites and govern the nuclear architecture by establishing chromatin boundaries. In this context, specific proteins that interact with and bind to MAR sequences called MAR binding proteins (MARBPs), are of paramount importance, as these sequences spool the proteins that regulate transcription, replication, repair and recombination. Recent evidences also suggest a role for these cis-acting elements in viral integration, replication and transcription, thereby affecting host immune system. Owing to the complex nature of these nucleotide sequences, less is known about the MARBPs that bind to and bring about diverse effects on chromatin architecture and gene function. Several MARBPs have been identified and characterized so far and the list is growing. The fact that most the MARBPs exist in a co-repressor/ co-activator complex and bring about gene regulation makes them quintessential for cellular processes. This participation in gene regulation means that any perturbation in the regulation and levels of MARBPs could lead to disease conditions, particularly those caused by abnormal cell proliferation, like cancer. In the present chapter, we discuss the role of MARs and MARBPs in eukaryotic gene regulation, recombination, transcription and viral integration by altering the local chromatin structure and their dysregulation in disease manifestation


title: Sepsis

text: Definition. „Sepsis“ ist eine systemische entzündliche Reaktion des Organismus (auch als SIRS bezeichnet, systemic inflammatory response syndrome) auf eine Infektion mit Bakterien, Viren, Pilzen und Parasiten. Bei der Sepsis ist die Reaktion des Organismus so heftig, dass es zu Temperaturerhöhungen, Tachykardie, Tachypnoe, Hypotension und disseminierter intravasaler Gerinnung kommen kann. Diagnostische Kriterien einer Sepsis im Kindesalter sind nach der International Sepsis Definitions Conference aus dem Jahr 2001: 1. Nachweis oder Verdacht auf eine Infektion, 2. Hyperthermie (>38,5°C) oder Hypothermie (<36,0°C), 3. Tachykardie, 4. Zeichen mindestens einer gestörten Organfunktion: a. Veränderung des mentalen Status, b. Hypoxie, c. erhöhte Laktatspiegel, d. veränderter Pulscharakter.


title: Stem Cell Transplantation

text: Hematopoietic cell transplantation (HCT) is associated with profound compromises in host defenses. The patterns of immune compromise change over time. Infections are an important cause of serious morbidity and pose substantial threats to life. Thus, the challenges of infection facing the transplant clinician are both myriad and dynamic. Early after transplant, neutropenic infections are most important. Later herpesvirus and invasive fungal infections predominate. Even late after transplant, patients with chronic graft versus host disease remain susceptible to encapsulated bacterial, varicella zoster virus, and invasive fungal infections. Over time, with robust engraftment and control of GVHD, the risk of serious infections recedes with immune reconstitution.


title: TB Matters More

text: Tuberculosis (TB) is the second leading infectious cause of mortality worldwide and arguably the most important neglected topic in bioethics. This chapter: (1) explains the ethical importance of TB, (2) documents its neglect in bioethics discourse, (3) maps the terrain of ethical issues associated with TB, and (4) advocates a moderate pluralistic approach to ethical issues associated with TB.


title: Delivery Systems for Lymphatic Targeting

text: The lymphatic system has a critical role in the immune system’s recognition and response to disease, and it is an additional circulatory system throughout the entire body. Most solid cancers primarily spread from the main site via the tumour’s surrounding lymphatics before haematological dissemination. Targeting drugs to lymphatic system is quite complicated because of its intricate physiology. Therefore, it tends to be an important target for developing novel therapeutics. Currently, nanocarriers have encouraged the lymphatic targeting, but still there are challenges of locating drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated colloidal carriers especially liposomes and solid lipid nanoparticles emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Optimising the proper procedure, selecting the proper delivery route and target area and making use of surface engineering tool, better carrier for lymphotropic system can be achieved. Thus, new methods of delivering drugs and other carriers to lymph nodes are currently under investigation.


title: Health Psychology

text: The chapter draws parallels and contrasts between the study of health in North American and other industrialized countries and health of people living in developing countries, which comprise 80% of the world’s population. Lessons are provided for three common health problems where psychologists play a major role within multidisciplinary teams. The lessons use published journal articles, web sites of international organizations, and the author’s personal experiences living and working in developing countries. One topic concerns the large number of women who unnecessarily die in childbirth and the non-medical reasons. The second is environmental health, which includes sources of clean water, waste disposal, and personal hygiene. Solving this problem requires behavior change. The third concerns child hunger and its disabling effects on cognitive development. The focus of this chapter is on examining the health problem within context and identifying solutions that work and do not work. Background is provided for the novice, so students learn the larger picture into which these issues fit, and how to apply the same analysis to other health problems.


title: Transfusiebeleid

text: Anesthesiologen en hematologen zijn in Nederland de grootste voorschrijvers van bloedproducten. Omdat het inzicht in de veiligheid en de indicaties voor bloedproducten de laatste jaren sterk is gewijzigd en omdat er nog steeds grote verschillen in voorschrijfgedrag bestaan tussen artsen en tussen ziekenhuizen, is het belangrijk om dit voorschrijfgedrag te harmoniseren. Up-to-date kennis over de ontwikkelingen in de transfusiegeneeskunde is daarom belangrijk.


title: The Interconnection between the Built Environment Ecology and Health

text: The built environment (BE) affects ecosystems, ecosystem services and human health and well being. While, formally, the BE ranges from the smallest hut to the largest city, this chapter focuses upon the health effects of urban areas, which increasingly are the preferred human habitat. Urban areas have many attractive and beneficial influences to human well-being. But at the same time, many effects of urban areas are harmful to well-being, and many are not even recognized as such. Most publications about these topics have described the effects of the BE separately, on either ecosystems or on human health. The interconnectivity between these two effects relative to BE is rarely studied. This paper focuses on the mutual influence and interactions between three related aspects of the BE which can impact ecosystems and human health: transportation, land use, and life style. It also explores some of the links between the BE, human health, and human security.


Respiratorische Erkrankungen


title: Terrorists and Social Media Messages: A Critical Analysis of Boko Haram’s Messages and Messaging Techniques

text: Post-colonial Nigeria has been plagued with violent conflicts. A bloody civil war in which an estimated 1 million people were killed ravaged the country from 1967 to 1970. Interethnic and intra-communal conflicts have also shaken the foundations of the nation since 1960 when colonial rule ended. Other violent conflicts that have plagued the country are religious conflicts in Kano, Bauchi, Kaduna, Kafanchan, Zaria, Jos, Maiduguri, and many other places. Blood-letting in the name of religion in these and other places in Nigeria has left thousands dead and wounded. Destruction of property in the course of religious violence in Nigeria has also wreaked economic calamity on the country. For instance, wanton destruction of property during the Maitatsene religious uprising in Kano from 1980 to 1985 resulted in the loss of lives and of millions of dollars. Clashes between members of the militant Shi’ite religious sect and the Nigerian army in 2016 led to the demolition of an entire neighborhood in Zaria city Nigeria’s latest bout of violence emanates from a deadly terrorist group, Boko Haram. Since 2009, it has killed over 20,000 people, displaced more than one million people, and contributed to the devastation of Nigeria’s northeast region. Initially, Boko Haram could not be contained by Nigerian security forces. It captured and held on to 14 local government districts and it constantly churned out online propaganda about its invisibility and its certainty that it would impose a radical Islamic government over the entire country. This chapter provides a critical analysis of Boko Haram’s propaganda. It examines the group’s core messages and the stylistic techniques used in delivering them. The chapter notes that Boko Haram deliberately used crude, unvanished imagery to reinforce the brutality of its actions in suicide bombings, drive-by shootings, and direct attacks against military barracks, markets, mosques, and churches. We contend that the effectiveness of Boko Haram’s propaganda began to decline as it suffered military defeats by Nigerian forces.


title: Biometrics and Knowledge Management Information Systems

text: Biometrics and knowledge management information systems are two important fields in recent years to attract wider attentions from different social groups. This chapter explores the use of hierarchical construction linking with biometrics applications and knowledge management information systems. The key issues are discussed and a sample case of information acquisition in content-based image retrieval system has been illustrated.


title: Viral Subversion of the Immune System

text: The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines.


Human Monoclonal Antibodies Against HIV and Emerging Viruses


Disease and Injury Among Veterinarians


title: Multiplex PCR for Detection and Identification of Microbial Pathogens

text: Multiplexed nucleic acid-based tests for infectious disease have become a standard part of clinical laboratory practice. These tests provide a comprehensive syndrome-based approach to determine the etiological agent of disease. The technology underlying these different systems is reviewed here with a special focus on the BioFire FilmArray® platform. The literature on the clinical utility and cost-effectiveness of these platforms for respiratory, blood culture, and gastrointestinal infections is discussed. Although there are reports showing a clear benefit to the patient or to the healthcare system from adopting a syndromic molecular approach, it is also apparent that clinical laboratories and healthcare providers are still learning how to take full advantage of the new systems. Finally, some improvements to this technology that should appear in the next few years are discussed. These include automated pathogen-specific surveillance based on aggregating the data from these systems, a move toward point-of-care syndromic testing, and further decreases in time to result of the tests.


title: Sore Throat

text: Approximately 12 million patients present with acute pharyngitis in the USA annually. Most episodes are viral; however, Group A streptococcus (GAS) is an important and treatable infection (Snow V, Mottur-Pilson C, Cooper RJ, et al., Ann Intern Med 2001;134:506). Group A streptococcus (GAS) is the most common bacterial etiology of acute pharyngitis and accounts for 15–30% of pharyngeal infections in children and 5–20% in adults. The goal of treatment is to reduce the duration and severity of symptoms, as well as reduce complications and transmission. Antimicrobial therapy is recommended for patients with a high index of suspicion for GAS pharyngitis or when it is confirmed by culture or rapid antigen detection testing (RADT). Overtreatment of acute pharyngitis is a major cause of inappropriate antibiotic use and can be avoided by using a systematic approach to evaluation and treatment (Snow V, Mottur-Pilson C, Cooper RJ et al., Ann Intern Med 2001;134:506.).


title: Indications for Liver Transplantation

text: Candidates for OLT must have irreversible acute or chronic end stage liver disease (table 41b.1). Virus or alcohol-induced liver cirrhosis constitute the most common disease indications in adults [1] (fig. 41b.1). In our department 28% of cirrhotic liver transplant recipients are transplanted for hepatitis C virus (HCV)-related liver disease and 26% undergo OLT for alcohol-related liver disease. Other indications include cholestatic liver disorders [primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), biliary atresia], hepatitis B virus (HBV) infection, autoimmune hepatitis, cystic fibrosis, inherited metabolic diseases (Wilson’s disease, hemochromatosis, alpha-1-antitrypsin deficiency), nonalcoholic steatohepatitis, nonmetastatic hepatocellular carcinoma, and acute virally-, toxin-, or drug-induced hepatic failure. The most common indications in children comprise biliary atresia and metabolic liver diseases


title: Clustering the Normalized Compression Distance for Influenza Virus Data

text: The present paper analyzes the usefulness of the normalized compression distance for the problem to cluster the hemagglutinin (HA) sequences of influenza virus data for the HA gene in dependence on the available compressors. Using the CompLearn Toolkit, the built-in compressors zlib and bzip2 are compared. Moreover, a comparison is made with respect to hierarchical and spectral clustering. For the hierarchical clustering, hclust from the R package is used, and the spectral clustering is done via the kLine algorithm proposed by Fischer and Poland (2004). Our results are very promising and show that one can obtain an (almost) perfect clustering. It turned out that the zlib compressor allowed for better results than the bzip2 compressor and, if all data are concerned, then hierarchical clustering is a bit better than spectral clustering via kLines.


Tuberculosis in the Intensive Care Unit


title: Human Respiratory Syncytial Virus: Biology, Epidemiology, and Control

text: According to the World Health Organization, acute lower respiratory tract infection (ALRI) is the fourth leading cause of death worldwide, responsible for approximately 3.1 million (5.5%) of the 56 million estimated deaths per year. Human respiratory syncytial virus (RSV) is recognized as the most important cause of ALRI in infants worldwide. It is estimated that every year 33.8 million new cases of RSV-related ALRIs occur and cause approximately 200,000 deaths in children younger than 5 years; of note, 99% of these deaths occur in developing countries. Usually primary infections occur during the first 2 years of life and are symptomatic, causing from mild upper respiratory tract illness to severe ALRI, and in some cases pneumonia and bronchiolitis may occur simultaneously. Recurrent infections throughout life are common but normally cause milder upper respiratory tract illness. Several studies also associated severe RSV infections during infancy with permanent lung function reduction in adulthood, with higher risk of asthma. The seasonality of the virus varies but it is often detected throughout the year. In South America the highest incidence occurs in the months of January to June. Despite the clinical importance and the disease burden associated with RSV, there is neither specific treatment nor vaccines widely accepted and available nowadays.


Food is Just One of Life’s Risks


title: Acute Kidney Injury (AKI)

text: Kidneys perform a multitude of essential functions within the human body. Of these the most important are (1) maintaining pH through regulation of acid/base levels and (2) excreting end products of metabolism. As for most organ-systems, these functions are especially important for healing following trauma and/or surgery and decline with age. Acute Kidney Injury (AKI) is one of the common forms of organ failures seen in the ICU and elderly patients are more prone to it. The causes maybe classified as Prerenal (inadequate perfusion), renal (inherent kidney disease) and post-renal (urinary obstruction). Preventing AKI should be an important concern in all critically ill patients but especially important in the elderly patients since the development of AKI can significantly increase in-hospital mortality. Once AKI has set in a systematic and step-wise approach of diagnosis and management is key to avoiding adverse outcomes.


title: Physical Environment of Tall Residential Buildings: The Case of Hong Kong

text: Increasing urban populations, scarcity of urban land, depletion in resources and severe impact of urban development on sustainability are critical contemporary issues. Such issues have vast implications on the desirability of compact, high-rise high-dense built forms. Yet, the environmental quality and social acceptance of these forms remain barely studied. This chapter reviews some of the critical environmental implications posed by the closely packed high-rise building and high urban densities.


title: Pulmonary Hemorrhage, Transient Tachypnea and Neonatal Pneumonia

text: In newborn infants, pulmonary hemorrhage, often a manifestation of pulmonary edema can range in severity from bloodtinged secretions in the endotracheal tube to life threatening blood loss with hypovolemic shock. It usually presents in the second to fourth day of life and may be associated with lung tissue damage (RDS, infection, and mechanical ventilation with high-inspired oxygen), hypoxia, hypervolemia, hypoproteinemia, congestive heart failure, and coagulation abnormalities. Klukow confirmed an association between pulmonary hemorrhage and a large patent ductus arteriosus with high pulmonary blood flow [1].


title: De immuungecompromitteerde patiënt

text: patiënten met aangeboren immuundeficiënties; patiënten met een langer bestaande neutropenie; patiënten met een hiv-infectie en een laag CD4-aantal (< 200); patiënten na een allogene hematopoëtische stamceltransplantatie; patiënten die afweerremmende medicatie ontvangen, bijvoorbeeld na een orgaantransplantatie.


title: The Multifunctional Nucleolar Protein Nucleophosmin/NPM/B23 and the Nucleoplasmin Family of Proteins

text: The nucleophosmin (NPM)/nucleoplasmin family of nuclear chaperones has three members: NPM1, NPM2, and NPM3. Nuclear chaperones serve to ensure proper assembly of nucleosomes and proper formation of higher order structures of chromatin. In fact, this family of proteins has such diverse functions in cellular processes such as chromatin remodeling, ribosome biogenesis, genome stability, centrosome replication, cell cycle, transcriptional regulation, apoptosis, and tumor suppression. Of the members of this family, NPM1 is the most studied and is the main focus of this review. NPM2 and NPM3 are less well characterized, and are also discussed wherever appropriate. The structure–function relationship of NPM proteins has largely been worked out. Other than the many processes in which NPM1 takes part, the major interest comes from its involvement in human cancers, particularly acute myeloid leukemia (AML). Its significance stems from the fact that AML with mutated NPM1 accounts for ∼30% of all AML cases and usually has good prognosis. Its clinical importance also comes from its involvement in virus replication, particularly in the era of outbreaks of infectious diseases.


title: Community-Acquired Pneumonia—Back to Basics

text: Lower respiratory tract infections are among the most common infectious diseases worldwide and are caused by the inflammation and consolidation of lung tissue due to an infectious agent.(1) The clinical criteria for the diagnosis include chest pain, cough, auscultatory findings such as rales or evidence of pulmonary consolidation, fever, or leukocytosis.


title: Modulation of Pre-mRNA Splicing Patterns with Synthetic Chemicals and Their Clinical Applications

text: Recent whole genome sequence analyses revealed that a high degree of proteomic complexity is achieved with a limited number of genes. This surprising finding underscores the importance of alternative splicing through which a single gene can generate structurally and functionally distinct protein isoforms [1]. Based on genome-wide analysis, 75% of human genes are thought to encode at least two alternatively spliced isoforms [2, 3]. The regulation of splice site usage provides a versatile mechanism for controlling gene expression and for the generation of proteome diversity, playing essential roles in many biological processes, such as embryonic development, cell growth, and apoptosis. The splice sites are generally recognized by the splicing machinery, a ribonuclear protein complex known as the spliceosome. Spliceosome binding is determined by competing activities of various auxiliary regulatory proteins, such as members of SR protein or heterogeneous nuclear ribonucleoprotein (hnRNP) protein families, which bind specific regulatory sequences and alter the binding of the spliceosome to a particular splice site [1, 4]. Pre-mRNA splicing is regulated in a tissue-specific or developmental stage-specific manner [5]. The selection of splice site can be altered by numerous extracellular stimuli such as hormones, immune response, neuronal depolarization, and cellular stress, through changes in synthesis/degradation, complex formation, and intracellular localization of regulatory proteins. SR proteins are heavily phosphorylated in cells and involved in constitutive and alternative splicing, and the phosphorylation states of SR proteins are altered in response to these extracellular stimuli [6]. Splicing mutations located in either intronic or exonic regions frequently cause hereditary diseases, and more than 15% of mutations that cause genetic disease affect pre-mRNA splicing [7]. Based on a hypothetical idea that we can cure human diseases by regulating the phosphorylation state of SR proteins with synthetic inhibitors of protein kinases, we started our long voyage to challenge the development of new chemical therapeutics.


title: Art and Heart

text: This study explores the perceptions and opinions of children toward the family. The analysis is based primarily on children’s drawings, interviews with children and observations on them, and literature review. The subjects of this study were 16 children from incomplete families, who participated in weekly drawing activities. In addition to the drawings by the children, data in the form of verbal descriptions and non-verbal expressions were collected throughout the drawing sessions via notes-taking, audio-taping, and photo-taking. The data were analysed to provide an understanding of the children’s definitions of the family, the functions of the family, the roles of the parents, what constitutes a “family member” in the minds of the children, the relationships and affection among family members, and the children’s expectations of the family. With such an analysis, it is hoped to explore the children’s perception of their family life, their feelings and emotions, and their outlook for the future. The children had many expectations and hopes concerning their family, home, family members including themselves, and society at large. They also had many dissatisfactions, even complaints. While the children had not discussed much about the functions of the family, they placed much importance on its emotional aspects, and they had expressed emotional needs for parents. In the eyes of the children from incomplete families, “Children’s Home” is a place that satisfies their daily living needs, but it is not family as it lacks affection. In sum, by letting the children speak their minds through their own drawings and interpretations, this study provides a fresh perspective from children on their views of family, family members, as well as the reality and fantasy of life.


title: Ontology Development for the Immune Epitope Database

text: A key challenge in bioinformatics today is ensuring that biological data can be unequivocally communicated between experimentalists and bioinformaticians. Enabling such communication is not trivial, as every scientific field develops its own jargon with implicit understandings that can easily escape an outsider. We describe here our approach to enforce an explicit and exact data representation for the Immune Epitope Database (IEDB Peters et al. 2005) through the use of a formal ontology. Being the first database of its scale in the immune epitope domain, it was necessary for the IEDB to devise an adequate data structure at the outset of the project with the goal that it should be capable of capturing the context of immune recognition. Early on, it became readily apparent that an unambiguous description of the information being captured is imperative for consistent curation across journal articles and among curators. Accordingly, an initial ontology was developed (Sathiamurthy et al. 2005) based upon consultations with domain experts and guidance from expert ontologists. The structure devised from this ontology proved capable of dealing with a great deal of immunological data over time.


title: Sensitivity of Model-Based Epidemiological Parameter Estimation to Model Assumptions

text: Estimation of epidemiological parameters from disease outbreak data often proceeds by fitting a mathematical model to the data set. The resulting parameter estimates are subject to uncertainty that arises from errors (noise) in the data; standard statistical techniques can be used to estimate the magnitude of this uncertainty. The estimates are also dependent on the structure of the model used in the fitting process and so any uncertainty regarding this structure leads to additional uncertainty in the parameter estimates. We argue that if we lack detailed knowledge of the biology of the transmission process, parameter estimation should be accompanied by a structural sensitivity analysis, in addition to the standard statistical uncertainty analysis. Here we focus on the estimation of the basic reproductive number from the initial growth rate of an outbreak as this is a setting in which parameter estimation can be surprisingly sensitive to details of the time course of infection.


Species-Neutral Disease Surveillance: A Foundation of Risk Assessment and Communication


title: Virus-Like Particles, a Versatile Subunit Vaccine Platform

text: Virus-like particles (VLPs) can be spontaneously formed after expression of self-polymerising viral capsid proteins. VLPs structurally resemble their native source virus, maintaining immunological relevance by retaining formation of immunogenic motifs with natural conformation. The absence of the virus genome renders VLPs safe for administration as a subunit vaccine. VLPs can target both arms of the immune response, with some VLPs initiating production of specific antibodies and others activating cytotoxic T cells. VLPs are also exceptionally versatile, conferring protection against the host virus or acting as a scaffold for antigenic molecules. In addition, VLP can support intraparticulate encapsulation for immunomodulation and gene delivery. VLP vaccines have been developed for prophylactic protection against infectious organisms, and therapeutic treatment of conditions such as Alzheimer’s disease, hypertension, and cancer. With an expanding list of vaccine candidates, VLP vaccines are a promising field with a wide range of applications.


title: Catastrophic Anachronisms: The Past, Present and Future of Disaster Medicine

text: Disasters, particularly earthquakes, volcanoes, floods, war-related complications, famine and infectious epidemics, have been a part of recorded human experience. From Pompeii to the Johnston Flood and World War II and the Black Plague to the Spanish Influenza, there have been catastrophic occurrences that will not long be forgotten by either legend or history books. Nevertheless, those occurrences were relatively few and far-between before the mid-twentieth century. Indeed, the nature of disasters has changed since then. From terrorists taking advantage of ‘new technology’ to weather-related events that cause trillions of dollars worth of damages and economic loss, the world has evolved.


title: Nierziekten

text: Gekenmerkt door hematurie, proteïnurie, hypertensie, oedemen en soms door oligurie en acute nierinsufficiëntie. Dit ziektebeeld verloopt sneller en heeft andere oorzaken dan ‘rapidly progressive’ *glomerulonefritis. Aet. Kan optreden zowel na bacteriële als na virale of parasitaire infecties. Meest bekend is *acute poststreptokokkenglomerulonefritis. Zeldzamere infectieuze oorzaken zijn: stafylokokken, pneumokokken, lues, waterpokken, mazelen, rubella, mononucleosis infectiosa, cytomegalievirus, hantavirus, hepatitis B en malaria. Andere oorzaken zijn *anti-GBM-glomerulonefritis en systeemziekten: *lupus erythematodes disseminatus, henoch-schönlein-nefritis (zie *Anafylactoïde purpura), *polyarteriitis, *granulomatosis van Wegener. Zie ook *Glomerulonefritis.


title: Emerging Risks Related to Food Technology

text: Global food security and safety are threatened by a number of fast-occurring changes, even in the absence of natural disasters or terrorist attacks: overpopulation and urbanisation, environmental pollution, climate changes, intensive animal breeding, international trade and travel, emerging water- and food-borne diseases, antimicrobial-resistant bacteria, increasing food costs, complexity of food supply chains, malnutrition and risky food behaviour. Food safety management tools, including food legislation, national and international standards, quality management systems, risk analysis, risk-based inspections and controls, monitoring and alert systems for food contaminants and food-borne diseases, quantitative microbial risk assessment, nutrition and toxicology studies, and elaborate food processing technologies have brought to consumers in developed countries a wide selection of safe foods. Predictive and early warning and communication systems are being developed to increase the ability to “expect the unexpected” and take prevention measures before food hazards become real risks. The production, processing, transportation, storage and/or distribution stages of modern food supply chains remain exposed to various types of biological or chemical contaminants, as evidenced by recent events or crises. The prion/BSE, dioxin, acrylamide, melamine, bisphenol A cases, and the numerous pathogen outbreaks illustrate this exposure. The melamine story and the international traffic of counterfeited foods and drinks show that profit-motivated fraud and adulteration are rising threats, opening potential paths for terrorist actions. Recent food preservation, processing or packaging technologies and trends, in spite or because of their benefits (mild treatment, extended product shelf-life, “fresher” quality, RTE pre-cooked convenience) also bring safety risks at the consumer level: incomplete microbial inactivation, possible non respect of adequate storage conditions and expiration dates, undercooking, and generation of stress-resistant micro-organisms. Innovative technologies, such as the use of nanoparticules in foods or food contact materials, and the development of active, intelligent or sustainable food packaging entail uncertainties and safety concerns. Natural disasters, droughts, floods, conflicts, and poverty often lead to emergency situations requiring large assistance operations with complex logistics and specific meals ready-to-eat or nutrient-supplemented foods. Containerised food processing units that could be deployed and quickly set to operate in production-disrupted areas are being developed by the World Food Programme. Other strategies against food insecurity include insurance policies for crop failures and renting of agricultural lands abroad. Citizen perception of food safety risks and the EU consumers’ “right to informed choice” explain why some technologies elicit rejection: ionising irradiation of foods, hormonal and antibiotic treatment of animals, the use of various “artificial” food additives, genetically modified crops and ingredients, cloned animals. Perceived benefits responding to consumers’ needs (healthier, more nutritive, higher quality, more convenient, lower cost), “naturalness”, respect of the environment and trusted information are the major factors influencing consumers’ acceptance of innovative food technologies and products. Novel foods and technologies are also subject to strict regulatory pre-market safety assessment and authorisation procedures. While necessary for protection against unexpected risks, some of these rules serve as barriers to innovation and trade, and fodder for strong political debates.


title: Animal Models for Reye’s Syndrome

text: Reye’s Syndrome (RS) was first documented by Douglas Reye and colleagues in 1963 as an “encephalopathy with fatty degeneration of the viscera,” a rare entity, but one that at that time was associated with an 80% mortality rate (Reye et al., 1963). Although the apparent incidence and outcome of the disease have improved, it continues to be one of the major causes of noninflammatory neurologic death after a viral illness in children (Sullivan-Boylai and Corey, 1981; Heubi et al., 1987).


title: Are We from Outer Space?: A Critical Review of the Panspermia Hypothesis

text: The biological record suggests that life on Earth arose as soon as conditions were favorable, which indicates that life either originated quickly, or arrived from elsewhere to seed Earth. Experimental research under the theme of “astrobiology” has produced data that some view as strong evidence for the second possibility, known as the panspermia hypothesis. While it is not unreasonable to consider the possibility that Earth’s life originated elsewhere and potentially much earlier, we conclude that the current literature offers no definitive evidence to support this hypothesis. Chladni’s view, that they fall from the skies, pronounced in 1795, was ridiculed by the learned men of the times. (Rachel, 1881) Evidence of life on Mars, even if only in the distant past, would finally answer the age-old question of whether living beings on Earth are alone in the universe. The magnitude of such a discovery is illustrated by President Bill Clinton’s appearance at a 1996 press conference to announce that proof had been found at last. A meteorite chipped from the surface of the Red Planet some 15 million years ago appeared to contain the fossil remains of tiny life-forms that indicated life had once existed on Mars. (Young and Martel, 2010)


title: Application of UPT-POCT in Anti-bioterrorism and Biosecurity

text: With the exception of toxins, bioterrorism agents are mainly microorganisms, many of which cause serious infectious diseases. Up-converting phosphor technology-based point-of-care testing (UPT-POCT) can detect bioterrorism agents from various samples with high sensitivity and specificity, in particular it shows robust performance for complicated samples, such as food, powder, viscera and grains. The tolerance of UPT-POCT to sample is based on the physical and luminescence stability of UCNPs, the stable covalent interaction between UCNPs and antibody, as well as the strong buffering capacity of the detection system. Reliable results can be obtained in a short time period using a portable biosensor by nonprofessionals owing to the simple nature of UPT-POCT operation and sample pre-treatment.


title: Thrombotic Microangiopathy Syndrome in the ICU

text: Since the first descriptions of haemolytic-uremic syndrome (HUS) by Moschowitz and thrombotic thrombocytopenic purpura (TTP) by Gasser, our knowledge about thrombotic microangiopathy (TMA) has grown considerably [1]. TMA now refers to a group of diseases comprising mechanical hemolytic anemia, peripheral thrombocytopenia, and varying degrees of organ failure. The incidence of TMA is increasing in the USA. Considerable progress has recently been made in the understanding of the pathophysiological mechanisms of TMA. These rare diseases, characterized by platelet thrombi in the microcirculation, are responsible for often serious organ dysfunction leading to the admission of these patients to intensive care units (ICUs). The prognosis of TMA was extremely poor prior to plasma therapy and especially plasma exchange. TMA is a serious, life-threatening disease that requires early diagnosis and urgent specialized therapeutic management.


title: Melanom

text: Das Melanom ist der gefährlichste Hautkrebs mit der höchsten Sterblichkeitsrate, der schon bei jungen Menschen auftreten kann und seit Jahrzehnten steigende Inzidenz verzeichnet (Jemal et al. 2007; Little et al. 2012). Jährlich erkranken weltweit etwa 137.000 Menschen am Melanom und 37.000 versterben an der Erkrankung (Boyle et al. 2004). Die Inzidenz liegt weltweit jährlich bei 2,3–2,6/100.000 Einwohner (Pisani et al. 2002). In Deutschland beträgt die Inzidenz 19,2/100.000 Einwohner und es verstarben 2711 Betroffene im Jahre 2010 (Statistisches Bundesamt).


title: Drug Resistance in Infectious Diseases: Modeling, Parameter Estimation and Numerical Simulation

text: Infectious diseases are drawing our attention again. In recent years, we have been confronted with SARS, bird-flu, swine-flu and many other severe diseases. In addition, pathogens are getting resistant to drugs controlling them. In this paper we establish a new population dynamical system of infectious diseases including drug treatment. We take into account both sensitive and resistant parasites. The unknown model parameters are fitted based on a set of data for malaria from Cisse, Burkina Faso. The fitted model is used to investigate the influence of drug treatment on drug resistance. Based on these investigations, treatment strategies to reduce drug resistance can be elaborated.


title: Surveillance and Seroepidemiology

text: Surveillance has been defined as the systematic collection of data pertaining to the occurrence of diseases, the analysis and interpretation of these data, and the dissemination of consolidated and processed information to contributors, programs, and other interested persons. A wide variety of data sources are used for surveillance purposes. Some data sources were designed for the purpose of surveillance while other data sources are used secondarily for surveillance. To improve the timeliness and quality of surveillance data while simultaneously minimizing cost, surveillance networks and Health Information Exchanges (HIEs) were developed. Surveillance networks allow developing countries to participate in surveillance, establishing early warning of outbreaks. HIEs facilitate access to and retrieval of patient clinical data to support more efficient, timely, effective, equitable, and safe healthcare and to enhance case reporting. Seroepidemiology is the systematic collection and testing of blood samples from a target population to identify current and past experiences with infectious diseases by means of biological markers. Data from serological surveys can reveal total burden of current and past, as well as apparent and inapparetnt infections. Surveillance and seroepidemiology have provided critical epidemiologic information to support public health policy at the local, national, and international levels.


title: Introduction: Climate Change, Human Security, and Violent Conflict in the Anthropocene

text: This book focuses on possible causal linkages among the three scientific research areas of climate change, human security, and violent conflict and asks whether they have posed challenges for societal stability in the past and in the present, and whether climate change might intensify societal instability in the future. It addresses scientific problems that are primarily analysed.


title: Online Social Networks Flu Trend Tracker: A Novel Sensory Approach to Predict Flu Trends

text: Seasonal influenza epidemics cause several million cases of illnesses cases and about 250,000 to 500,000 deaths worldwide each year. Other pandemics like the 1918 “Spanish Flu” may change into devastating event. Reducing the impact of these threats is of paramount importance for health authorities, and studies have shown that effective interventions can be taken to contain the epidemics, if early detection can be made. In this paper, we introduce Social Network Enabled Flu Trends (SNEFT), a continuous data collection framework which monitors flu related messages on online social networks such as Twitter and Facebook and track the emergence and spread of an influenza. We show that text mining significantly enhances the correlation between online social network(OSN) data and the Influenza like Illness (ILI) rates provided by Centers for Disease Control and Prevention (CDC). For accurate prediction, we implemented an auto-regression with exogenous input (ARX) model which uses current OSN data and CDC ILI rates from previous weeks to predict current influenza statistics. Our results show that, while previous ILI data from the CDC offer a true (but delayed) assessment of a flu epidemic, OSN data provides a real-time assessment of the current epidemic condition and can be used to compensate for the lack of current ILI data. We observe that the OSN data is highly correlated with the ILI rates across different regions within USA and can be used to effectively improve the accuracy of our prediction. Therefore, OSN data can act as supplementary indicator to gauge influenza within a population and helps to discover flu trends ahead of CDC.


title: Origins of the regulated secretory pathway

text: Modes of transport of soluble (or luminal) secretory proteins synthesized in the endoplasmic reticulum (ER) could be divided into two groups. The socalled constitutive secretory pathway (CSP) is common to all eukaryotic cells, constantly delivering constitutive soluble secretory proteins (CSSPs) linked to the rate of protein synthesis but largely independent of external stimuli. In regulated secretion, protein is sorted from the Golgi into storage/secretory granules (SGs) whose contents are released when stimuli trigger their final fusion with the plasma membrane (Hannah et al. 1999).


title: Prophylaxis of Healthcare Workers in an Influenza Pandemic

text: The threat of an imminent influenza pandemic has galvanized global efforts to identify effective preparedness strategies and consider securing health resources. As the nations prepare to meet this threat, public health interventions are being carefully gauged within the context of influenza epidemiology, populations, and healthcare systems. A pandemic will place enormous demands on healthcare systems that include at the center of planning efforts the protection of healthcare workers. During an influenza pandemic, healthcare workers will be on the front lines delivering care to patients and preventing further spread of the disease. Protecting these workers from acquiring or transmitting infection in the hospital ward and outside the workplace is critical to containing a pandemic and limiting morbidity and mortality of the population. Several approaches to protecting healthcare workers include vaccination, antiviral 10.1007/978-0-387-78665-0_6443, use of personal protective equipment, and adherence to other infection control practices. In the absence of vaccination, application of antiviral drugs has been rationalized as the first-line defense against the 10.1007/978-0-387-78665-0_6288. While the treatment of ill individuals is top priority in most national contingency plans, the use of drugs as prophylaxis has been debatable. This chapter attempts to highlight the importance of a competent healthcare system in response to an influenza pandemic, and presents the conflicting issues that are surrounding an antiviral prophylaxis strategy. An overview of potential benefits and limitations, logistical constraints, and clinical and epidemiological consequences of healthcare worker prophylaxis is also provided.


title: Pulmonary Complications of Obstetric and Gynecologic Conditions

text: The respiratory and the female reproductive systems are not embryologically or functionally related. However, the reproductive system can exert significant effects on the respiratory system as a result of the various hormonal changes that occur during a woman’s menstrual cycle and especially during pregnancy. In addition, there are several unique gynecologic and/or obstetric conditions that can directly affect the respiratory system. The following chapter reviews the effects of pregnancy on the respiratory system, as well as the special issues concerning the management of common respiratory conditions (e.g., pneumonia, asthma) during pregnancy. In addition it reviews several gynecologic disorders with unique pulmonary complications.


Schweinebandwurm


title: Epidemiology of Acute Respiratory Failure and Mechanical Ventilation

text: Acute respiratory failure, and the need for mechanical ventilation, remains one of the most common reasons for admission to the intensive care unit (ICU). The burden of acute respiratory failure is high in terms of mortality and morbidity as well as the cost of its principal treatment, mechanical ventilation. Very few epidemiologic studies have evaluated the prevalence and outcome of acute respiratory failure and mechanical ventilation in general. Most of the published literature has focused on specific forms of acute respiratory failure, particularly acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this chapter, we provide a brief review of the pathophysiology of acute respiratory failure, its definition and classification, and then present the incidence and outcomes of specific forms of acute respiratory failure from epidemiologic studies.


title: Network-Based Analysis of Beijing SARS Data

text: In this paper, we analyze Beijing SARS data using methods developed from the complex network analysis literature. Three kinds of SARS-related networks were constructed and analyzed, including the patient contact network, the weighted location (district) network, and the weighted occupation network. We demonstrate that a network-based data analysis framework can help evaluate various control strategies. For instance, in the case of SARS, a general randomized immunization control strategy may not be effective. Instead, a strategy that focuses on nodes (e.g., patients, locations, or occupations) with high degree and strength may lead to more effective outbreak control and management.


title: Counteraction to CBRN Terrorism in Switzerland

text: In Switzerland, the planning of security policy measures now increasingly factors in scenarios involving the use of CBRN weapons on Swiss soil. While there have been no terrorist “spectaculars” or dramatic news reports in recent years, this does not mean that the CBRN threat has diminished. In 2003 a project called National NBC Protection was started in order to guarantee efficient coordination of all partners involved in CBRN prevention and incident management at all levels with the aim of improving the NBC protection in Switzerland in the long term. The availability of outstanding expertise in terms of NBC protection therefore remains as important as ever for the Swiss population.


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

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


title: 2 Infecties van de bovenste luchtwegen

text: Luchtweginfecties in het algemeen en infecties van de bovenste luchtwegen in het bijzonder komen wereldwijd zeer veel voor en zijn de voornaamste reden om een arts te consulteren.


title: Biosafety and Bioethics

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


title: 7 Hoesten, van symptoom tot diagnose

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


title: Broncopneumopatia cronica ostruttiva (BPCO)

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