title: Laryngitis, Tracheitis, Epiglottitis, and Bronchiolitis: Sore Throat, Change in Voice, Feverora Wheezing Infant in Respiratory Distress

text: The middle and lower respiratory tract is a very common location for infections in infants and children. Infections of the mucosal surfaces of the larynx, trachea, and bronchial tree account for the majority of all infections in this age group and can be associated with considerable morbidity and even mortality in certain populations. Many viral upper respiratory tract pathogens can also involve the middle and lower respiratory tract, particularly for children experiencing their first infection with the pathogen. Laryngitis may cause sore throat and hoarse voice but can also be associated with tracheitis and even bronchiolitis as the pathogen, infection, and host responses move further down the respiratory tree. Bronchiolitis may also occur as a separate infection in the lower airways presenting as respiratory distress in a young infant with prominent wheezing. Many respiratory viral diseases occur with seasonal patterns, with most cases occurring in the fall, winter, and early spring in temperate climates. In the tropics, some viruses, such as respiratory syncytial virus (RSV), may cause disease sporadically, year round, but epidemics still occur during “rainy” seasons. Bacterial infections can also involve the middle airway. Epiglottitis is a feared condition due to the potential for sudden airway obstruction. Fortunately, the diagnosis of epiglottitis has become quite rare since the introduction of routine childhood immunization against Haemophilus influenzae, serotype B, was once the most common cause of epiglottitis. Bacterial tracheitis can be a secondary bacterial infection following an acute viral infection of the trachea or a consequence of prolonged endotracheal intubation. While the mechanism of injury to the trachea is different, both processes lead to disruption of mucosal integrity, predisposing the patient to a tracheal infection caused by bacteria that normally only colonize the airway.


title: Water Quality: Mindanao Island of the Philippines

text: The Philippines is an archipelagic country dominated by water and inland water sources. Water quality has been the subject of attention for the country and specifically, Mindanao Island, because of the role this natural resource plays in agriculture. Water supply and usage for the island and the nation are identified and discussed in relation to the scarcity of potable water. Potential threats and pollution hotspots bring forth the various health and environmental impact attributed to the water system accessibility, distribution, and quality. Strategies addressing water resources problems are taken into consideration side-by-side the numerous national laws, policies, standards, and guidelines in addressing water quality control and management. Therefore, the legal framework for various agencies to carry out these policies on quality control, usage, and water management are pivotal to recommendations on revision of certain provisions that rely on embedding local community involvement to lessen the environmental impact that is causal to poor population health. The World Bank has been instrumental in prompting local activity with initiatives first established in relation to the United Nations Millennium Development Goals that are being carried forward today in the Sustainable Development Initiatives. This chapter extends the recent UN and World Bank initiatives to demonstrate how further community involvement can continue to improve quality of life for Philippine citizens through education and participation.


title: Pharyngitis and Pharyngeal Space Infections: fever, sore throat, difficulty swallowing

text: Pharyngeal infections are very common in patients of all ages. They are typically associated with a sore and swollen throat that makes it difficult for the patient to swallow. They may also be accompanied by fevers, swollen lymph nodes, cough, voice hoarseness, and classic symptoms of an upper respiratory infection such as rhinorrhea. The majority of these infections are benign and run a self-limited course, although they often cause patients significant discomfort. A small but still significant number of cases will be due to a more serious process, such as a deep neck space infection. It is important to recognize the clinical and radiographic differences between these patients and patients with simple pharyngitis and triage them appropriately. Failure to recognize and treat patients with more serious infections can have dire consequences and can lead to increased morbidity and mortality. It is also important to recognize that certain populations of patients will be more susceptible to atypical infections. Specific conditions, particularly those that lead to immunocompromise, should prompt the clinician to expand their differential and consider atypical causes of pharyngeal infections.


title: The Catastrophic Antiphospholipid Syndrome

text: The addition of the word “catastrophic” to the term antiphospholipid syndrome (APS) was proposed 20 years ago by Ronald Asherson when he published an editorial in The Journal of Rheumatology describing a group of patients who develop multiple thrombosis in a short period of time and with a much worse prognosis than that attributed to patients with classic APS [1]. Since then, many cases have been published reporting patients with this devastating variant of the APS.


title: The Diffusion of the Black Death and Today’s Global Epidemics

text: It was the eminent mathematician Daniel Bernoulli (Bernoulli, Mémoires de l’Académie Royale des Sciences – Histoire Année, Imprimerie Royale, Paris, 1766) from Basel who had the idea of describing the development of an epidemic using a differential equation, in particular with the aim of showing how the epidemic could be mitigated by vaccination.


title: Otitis, Sinusitis, and Mastoiditis: Ear or Facial Pain Following a Common Cold

text: Otitis, sinusitis, and mastoiditis represent a range of common upper respiratory tract infections that are more common in children than in adults. The clinical presentation of otitis varies based on the anatomic site of disease. Acute otitis media and otitis media with effusion are infections of the middle ear, and otitis externa is infection of the external auditory canal. Otitis is one of the most common infections seen in young children. Each case represents an opportunity to practice precise diagnostic skills and to practice judicious antibiotic use. Sinusitis, while also relatively common, may present with nonspecific signs and symptoms. An accurate diagnosis requires a complete history and careful physical examination to help distinguish between viral rhinosinusitis, a condition that is usually self-limiting, and bacterial rhinosinusitis, a condition that requires treatment with antibiotics. Mastoiditis is a less common condition that can occur as a complication of otitis media. Prompt recognition and appropriate antibiotic treatment, often in combination with surgical debridement, is required to prevent further spread of the infection and the development of secondary complications.


Pneumonien


title: Epigenetic Significance of Chromatin Organization During Cellular Aging and Organismal Lifespan

text: Aging is a developmental process that occurs through epigenetic reprogramming that involves nine hallmark characteristics, most notably genomic instability. During physiological development, chromatin is modified, reorganized, and de-compacted in order for DNA to be transcribed, replicated, and repaired. The most prominent histone modifications include acetylation, methylation, ubiquitylation, ADP-ribosylation, phosphorylation, and sumoylation. Younger cells/tissues are characterized by greater global methylation. Global DNA demethylation in aging occurs mainly at repetitive DNA elements and in genome regions with facultative heterochromatin, which leads to overall deheterochromatinization of the genome.


title: Biologie

text: Zunächst wird die erdgeschichtliche Entwicklung des Lebens behandelt, auch die Frage, ob es außerirdisches Leben auf fremden Planeten gibt. Im Zentrum steht die Frage nach dem Werden des Menschen als letztes Glied der Homininen. – Um die Genetik darzustellen zu können, werden Bau und Funktion der lebenden Zelle behandelt. Die in jedem Zellkern liegenden Molekülketten sind jene Gene, die die Erbinformation beinhalten. Mit ihnen wird über den Genetischen Code die Bildung der lokalen Gewebeproteine gesteuert. Auf die Vererbungsfolge gentechnisch Einfluss nehmen zu können, löst bei vielen Menschen Besorgnis aus. –Wegen ihrer Bedeutung wird auf die bei Viren- und Bakterienbefall beruhenden Gefahren eingegangen. – Mit dem auf C. DARWIN zurückgehenden historischen und heutigen Verständnis des Evolutionsprinzips und seiner Implikation mit der religiösen Deutung des Lebens endet das Kapitel.


title: Moderne Anwendungsbeispiele aus der Elektrophysiologie

text: Alle Verfahren, die wir bisher diskutiert haben, Flussmessungen, Messungen von stationären und transienten Strömen und die entsprechenden Auswert¬verfahren können genutzt werden, um Funktion, Regulation und Struktur-Funktionsbeziehungen zu analysieren. Solche Informationen können wir gewinnen, indem wir die Funktionen von chemisch oder genetisch modifizierten Carriern oder Kanälen charakterisieren und miteinander vergleichen. Letzteres gilt auch für natürlich auftretende Mutationen, die Ursache für verschiedene Krankheiten sein können; die mit den genannten Methoden gewonnenen Erkenntnisse sind wichtiger Bestandteil für das Verständnis und die Behandlung solcher Krankheiten. Für viele der Transportproteine konnte die Aminosäuresequenz und die mögliche Orientierung des Proteins in der Membran ermittelt werden, oder es konnte sogar die dreidimensionale Struktur bestimmt werden. Im Folgenden wollen wir die Vorgehensweise eines Elektrophysiologen an Beispielen illustrieren, um Struktur, Funktion und Regulation von Membrantransport zu untersuchen. Für das Verständnis der Wirkung chemischer Stoffe sowie die Entwicklung neuer Medikamente zur Behandlung von Krankheiten stellt die Elektrophysiologie eine leistungsfähige Methode bereit, um die Wechselwirkung solcher Substanzen mit ihren Rezeptoren zu erforschen. Dieses soll beispielhaft an viralen Ionenkanälen illustriert werden.


title: Parasites and Diseases

text: The Antarctic krill Euphausia superba is among the most studied species of the Order Euphausiacea in biological and ecological aspects; however, reports of their parasites and diseases are relatively scarce. A worldwide overview of all parasites known for 48 out 86 extant euphausiid species includes 17 distinct types of epibionts, pathogens, parasites, and parasitoids. So far, only seven of them have been reported interacting with E. superba [epibionts: exuviotrophic ciliates (Foettingeriidae) and microplanktophagous ciliates (Suctoridae, Ephelota), pathogens: chitinoclastic bacteria and fungi; and trophically transmitted endoparasites: Apicomplexans (Gregarinidae, Cephaloidophora), nematode infecting krill’s eggs (under laboratory conditions), and histophagous parasites: Apostomatida ciliates of the family Pseudocollinidae]. The epibionts have interspecific associations that strongly depend on the krill’s moult cycle, discarding them at each moulting event. Their colonization and intensity show a remarkable synchronization with the krill moulting process at individual, school, and population levels. The social and sometimes highly dense swarms and schools of E. superba, its keystone trophic function (both as voracious predator and as prey to multiple predators) should make it a critical vector for trophically transmitted parasites in the food web. However, E. superba interacts with a relatively low diversity of epibionts, pathogens, and parasites, in comparison with parasite diversity known for relatively well-studied temperate (Meganyctiphanes norvegica, Euphausia pacifica) and subtropical (Nyctiphanes simplex) euphausiid species. The apparently low parasite diversity of E. superba is likely associated with its Antarctic zoogeographic pattern; where, parasites have not invaded the Antarctic krill with the same evolutionary success as have occurred with other euphausiid species from tropical, subtropical, temperate, and even Arctic ecosystems.


title: Molecular basis of genetic variation of viruses: error-prone replication

text: Genetic variation is a necessity of all biological systems. Viruses use all known mechanisms of variation; mutation, several forms of recombination, and segment reassortment in the case of viruses with a segmented genome. These processes are intimately connected with the replicative machineries of viruses, as well as with fundamental physical-chemical properties of nucleotides when acting as template or substrate residues. Recombination has been viewed as a means to rescue viable genomes from unfit parents or to produce large modifications for the exploration of phenotypic novelty. All types of genetic variation can act conjointly as blind processes to provide the raw materials for adaptation to the changing environments in which viruses must replicate. A distinction is made between mechanistically unavoidable and evolutionarily relevant mutation and recombination.


title: Select agent regulations

text: Several events over the past two decades have changed the way scientists acquire and work with pathogenic microorganisms and toxins in the United States and internationally. The Select Agent Regulations, which were promulgated by CDC and APHIS to address concerns raised by these events, have been in effect for more than 20 years. Knowledge of these and other regulations that will impact the practice of microbial forensics is essential.


title: Understanding the Microfoundations of Government–Civil Society Relations

text: This article adds a much needed microlevel perspective to the literature on interactions between civil society organizations and governments. I argue that a microlevel perspective assists in making connections between two dominant streams in the literature on government–CSO relations: an empirical–analytical stream and a critical stream. It aims to better understand the interactions and relations, by analysing the institutional work done by CSOs’ members. Adopting this approach puts CSO members in a more agentic position. Interactional processes are brought to the centre of analysis. The Dutch Community Sport Coach programme was used as a case to illustrate the usefulness of the approach. Through a one-year organizational ethnography, the article scrutinizes the way in which members of one CSO enact the organization’s service delivery relationship with a municipality. Through a multidimensional perspective on agency, the analysis shows how individual CSO members act as embedded agents that assimilate a public logic into the dominant community logic. It further shows the CSO’s members efforts and struggle to maintain their community logic. The article argues that an analysis of the microfoundations of government–civil society organization relations foregrounds the multivocality of the relationship as foundational.


title: Intelligence and Stakeholders

text: This chapter underscores the need for more explicit and strategic engagement of stakeholders (scientists, clinicians, first responders, amongst others) by the intelligence community. The chapter argues that the intelligence community will increasingly rely on their expertise to build more valid and reliable assessments of emerging bio-threats and risks. However, the discussion also identifies some of the limitations and challenges stakeholders themselves have to understanding complex threats and risks.


title: Infectieziekten in de mondzorgpraktijk

text: Van een groot aantal infectieziekten is bekend dat ze in de setting van de mondzorgpraktijken besmettelijk kunnen zijn. Behalve de ‘huis-tuin-en-keuken’ ziekten zoals verkoudheden en griepachtige varianten, gaat het in een aantal gevallen om buitengewoon besmettelijke of soms ook zeer ernstige infectieziekten. Zowel het team van mondzorgverleners als de patiënten kunnen een besmetting oplopen tijdens of aansluitend aan tandheelkundige behandelingen. Met de standaardmaatregelen voor infectiepreventie in mondzorgpraktijken is het besmettingsrisico rondom de behandelingen tot een aanvaardbaar niveau terug te dringen en hoeven slechts in een beperkt aantal gevallen extra beschermingsmaatregelen genomen te worden om besmettingen tegen te gaan. In dit hoofdstuk worden de belangrijkste infectieziekten besproken die tijdens behandelingen in de mondzorgpraktijk een besmettingsgevaar opleveren.


title: Immunology and Medical Microbiology

text: We are continuously exposed to many pathogens through inhalation, ingestion, and touch. The immune system protects us from the majority of these pathogens as flatworms, bacteria, fungi, and viruses. We have also witnessed tremendous progress in the prevention and treatment of infectious diseases; still, they remain a major challenge and are responsible for major cause of death and disability worldwide. The immune system’s memory response and vaccination have resulted in complete eradication of many diseases. Our immune system is very adaptive and consists of a variety of cells and molecules, which play an active role in protecting us. It not only protects us from the outside pathogenic agents but also is also capable of recognizing the body’s own components. It recognizes them as self and does not induce response against them. It is known as self-/non-self-discrimination. Sometimes due to certain defects or other reasons when the immune system is not able to differentiate self, then it mounts an attack on self-components leading to autoimmunity. The importance of the immune system was recognized by early work of Dr. Edward Jenner and Louis Pasteur; they recognized the abilities of the immune system, and since then the system was gradually being explored and it laid the foundation of immunology. However, day-by-day microbes are also posing health risks as new strains are continuously being evolved. Many chemotherapeutic agents have been developed to control the spread and infections. However, microbes are also continuously developing the ability of their survival with emergence of new strains and properties. Antibiotic resistance is occurring with all classes of microbes posing a serious clinical problem in managing infections. The diseases like tuberculosis, cholera, and rheumatic fever, which were believed to be eradicated, have ferociously reemerged. The reemergence and new pathogenic agents might be the result of mutations in their genome and changes occurring in the environment. In this chapter, basic concept of the immune system and some of the diseases of the skin, gastrointestinal tract, nervous system, and respiratory system caused by microorganisms are discussed along with sexually transmitted diseases and characterization of pathogens.


title: Categories of Morbidity Data

text: Medical science relies on classification systems in order to understand the nature of morbidity, and a number of classifications systems are utilized in healthcare. Epidemiologists, medical practitioners, and healthcare administrators must be able to place health conditions into appropriate categories for a variety of reasons. Most existing classification systems were established to facilitate the diagnostic process but have subsequently come to be used for administrative, planning, and fiscal management purposes. Chapter 10.1007/978-1-4939-3423-2_3 provides an overview of the ways in which morbidity data can be categorized, the ways different parties view and utilize the data, and the various official classification systems that are used in health care and other arenas.


title: Intravasale infecties en sepsis

text: Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties genoemd. De circulatie van bloed door het hart is essentieel voor de aanvoer van zuurstof en voedingsstoffen naar weefsel en organen en voor de afvoer van afvalstoffen. In principe bevat het intravasale systeem geen micro-organismen. Bloed is steriel. Als micro-organismen in de bloedbaan komen, worden ze snel verspreid, hetzij vrij in plasma, hetzij gehecht aan of in de bloedcellen. Binnen twee minuten bereiken ze dan een capillair systeem waarin ze kunnen achterblijven. In weefsels en organen kunnen ze soms aan specifieke cellen hechten (tropisme) en na groei specifieke infecties van die weefsels of organen veroorzaken (bijv. hepatitis B-virus in de lever, meningokokken in de meningen). Andere micro-organismen veroorzaken infecties door in het bloed of in de cellen in het bloed (bijv. plasmodiumsoorten, de oorzaak van malaria), in bloedvaten of in het hart te groeien. Deze infecties worden intravasale infecties genoemd. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_14) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.


title: China’s Aid to Africa’s Fight Against Ebola

text: In 2014, the Ebola virus disease outbreak spread through West African countries. The Chinese Government took early action and initiated multiple rounds of aid, which so far comprises the largest and longest humanitarian and health aid initiative in China’s history. By the first half of 2015, the Chinese Government had delivered four rounds of humanitarian aid against Ebola totaling 750 million RMB of funding. The fifth round of aid, which focuses on post-Ebola reconstruction and long-term public health system strengthening, is ongoing. China’s fight against Ebola in Africa manifested the principles of “sincerity, real results, affinity and good faith” that guide China’s policy on Africa and China’s view on global responsibility and security as a major power. China drew on its experience during the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 and adopted a comprehensive aid scheme with “hard” and “soft” aid aiming at both long- and short-term goals, with relevant departments working closely together and adopting flexible measures. China also strengthened its coordination and cooperation with international partners, and attached importance to public communication and information disclosure. The following results were achieved: (1) China made a tremendous contribution to controlling the epidemic and local capacity-building while realizing the goal of zero infection of Chinese personnel; (2) by exerting the expertise and organizational advantage of military health institutions, China achieved greater effectiveness and efficiency and strengthened bilateral trust; and (3) China improved its biosecurity capacity and established an important platform for tropical infectious disease research and real-time monitoring of global infectious disease epidemics.


title: Explanation of Metastasis by Homeostatic Inflammation

text: If inflammation caused by either non-self or self molecules can disseminate throughout the body and inflammatory sites actively allow entry of circulating tumor cells and assist regrowth, then circulating tumor cells metastasize to the sites of inflammation. However, disrupted sites of homeostatic inflammation do not necessarily guarantee metastatic spread and subsequent regrowth.


title: Biotechnology for Wildlife

text: Wildlife is of paramount significance to welfare of humans. In modern era, the wild animals are the sources of income, food, fur, micro-organisms, and other products besides its role in maintaining ecological balance. Shrinking habitat, diseases and pest prevalence, and illegal hunting are the major threats due to which many wild species have become extinct and many are endangered. Scientific interventions are being used to not only harnessing the potential of wildlife, but conserving them through assisted reproduction, genomics, and public awareness. Key points: Wildlife is an essential component of natural ecosystem . Wild natural flora and fauna are declining rapidly. Biotechnological interventions should be used conserve and increase wild animals.


title: Anwendungsgebiete für rekombinante Antikörper

text: Antikörper werden seit Jahrzenten in zahlreichen unterschiedlichen Assays eingesetzt. Der wohl meistverbreitete Assay in der Forschung und Diagnostik ist der Immunblot, auch häufig als Westernblot bezeichnet. Hier werden zuerst Proteine mittels SDS-PAGE aufgetrennt, dann auf eine Nitrocellulose- oder PVDF-Membran übertragen und die nachzuweisenden Proteine mit Hilfe eines Detektionsantikörpers gefärbt.


title: Zoönosen

text: Een zoönose is een infectieziekte die van dier op mens kan overgaan of andersom. Mensen komen op diverse manieren in contact met dieren. Zo heeft 55 % van de Nederlandse gezinnen één of meer huisdieren, heeft Nederland een hoge dichtheid aan voedselproducerende landbouwhuisdieren en kunnen mensen in contact komen met dieren in het wild tijdens buitenactiviteiten. De contacten tussen mens en dier kunnen direct zijn, door aanraking, aanhoesten, likken of bijten, of indirect door contact met feces of urine, inhalatie van stof met besmette excreta, contaminatie van het milieu, het eten van besmet voedsel of via een vector. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_18) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.


title: Entertainment Distribution Decisions

text: With digitalization having dramatically reshaped entertainment distribution, this chapter sheds light on three fundamental distribution-related issues that entertainment managers are dealing with today. Regarding the timing of a new product’s initial release, we show that descriptive statistics on the commercial potential of certain release periods are misleading, as they combine demand-sided influences with supply-sided effects caused by managers themselves. Furthermore, managers must thoroughly orchestrate the plethora of distribution channels that exist today. We introduce a framework of the macro- and micro-level factors that need to be considered when valuing alternative distribution models and report results from empirical scholarly experiments on sequential distribution. Finally, we study the piracy threat: its importance, its determinants, and the effectiveness of anti-piracy measures.


title: Progressive Adaptation: The Key to Sustaining a Growing Global Population

text: Adaptation is an evolving long-term process during which a population of life forms adjusts to changes in its habitat and surrounding environments. Adaptation by the global community as a unit is vital to cope with the effects of increasing populations, global warming/climate change, the chemical, biological, and physical impacts on life-sustaining ecosystems, and competition for life sustaining and economically important natural resources. The latter include water, food, energy, metal ores, industrial minerals, and wood. Within this framework, it is necessary to adapt as well to changes in local and regional physical conditions brought on by natural and anthropogenic hazards, by health threats of epidemic or pandemic reach, by social conditions such as conflicts driven by religious and ethnic fanaticism, and by tribalism and clan ties.


title: Polymer-Based DNA Delivery Systems for Cancer Immunotherapy

text: The use of gene delivery systems for the expression of antigenic proteins is an established means for activating a patient’s own immune system against the cancer they carry. Since tumor cells are poor antigen-presenting cells, cross-presentation of tumor antigens by dendritic cells (DCs) is essential for the generation of tumor-specific cytotoxic T-lymphocyte responses. A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter summarizes the physicochemical properties and biological information on polymer-based non-viral vectors used for targeting DCs, and discusses the main challenges for successful in vivo gene transfer into DCs.


title: Aminoaciduria and Glycosuria in Children

text: Only negligible amounts of amino acids and glucose are normally present in the final urine, reflecting very efficient reabsorption mechanisms for these organic solutes in the proximal tubule. Renal tubular transport defects or specific metabolic abnormalities result in excretion of significant quantities of amino acids or glucose in the urine. Although hereditary defects in renal tubular transport of most of these substances are uncommon, they are of major biologic importance. First, some of these membrane transport disorders (e.g., cystinuria, lysinuric protein intolerance, Hartnup disease) are associated with significant morbidity. Second, the study of these disorders has provided much insight into the physiology of renal tubular reclamation of amino acids and glucose and into the specific metabolic pathways that control their reabsorption and has been crucial in understanding the genetics of tubular transport systems.


title: Concurrence of Tuberculosis and Other Major Diseases

text: The chronic respiratory disease of tuberculosis (TB) has become one of the most significant infectious diseases because of its high mortality. It also results in serious social and economic problems that challenge global public health. Anti-TB treatment has achieved satisfactory results; however, concurrence with other diseases such as diabetes, silicosis, malnutrition, or immunosuppressive therapy can significantly interfere with the treatment of TB. Though irregular treatment is the overriding cause of treatment failure, drug-resistant TB or severe TB and complications are also significant factors. Respiratory tract infection and respiratory failure are the leading cause of death for TB.


title: Infecties bij patiënten met een gestoorde afweer

text: De eerste verdedigingslinie, gevormd door het intacte oppervlak van huid en slijmvliezen, is van groot belang voor de afweer tegen micro-organismen. De kwaliteit van deze verdedigingslinie kan worden aangetast door een fysisch of chemisch trauma, waardoor micro-organismen hun kans schoon zien. Ook de processen die bijdragen tot de kwaliteit van deze verdedigingslinie, zoals secretie (o.a. talg, zweet, mucus, maagzuur) en beweging (trilhaaractiviteit, darmmotiliteit en blaaslediging) kunnen worden aangetast. Iatrogene schade aan de eerste verdedigingslinie is niet zeldzaam: injecties, operaties, katheterisaties en medicamenteuze interventies (o.a. antacida, parasympathicolytica, morfinomimetica) kunnen de afweer in negatieve zin beïnvloeden. Hoewel de eerste verdedigingslinie van groot belang is, zal dit hoofdstuk zich vooral richten op een aantal stoornissen in de overige verdedigingslinies, namelijk de humorale en de cellulaire afweer. Afhankelijk van de soort afweerstoornis komen bepaalde infecties voor; omgekeerd kan men aan de hand van de soort infecties die men ziet dikwijls een voorspelling doen over de aard van de afweerstoornis.


title: TCM

text: Weil die Wissenschaft erkannt hat, dass schon der „banale“ Infekt bei Prädisponierten die Sensibilisierung erleichtert und bei Allergikern zu akuten Exazerbationen mit Etagenwechsel und Chronifizierung führen kann, soll nun ein Bogen über fast 2000 Jahre gespannt werden – von der aktuellsten Grundlagenforschung des 21. Jahrhunderts zur Weisheit des Klassikers der TCM „Shānghán zábìng lùn“ von 200 n. Chr. Dieser Klassiker setzt sich systematisch mit dem Ursprung und der Entwicklung von Kälte-induzierten Krankheiten und Behandlungsmöglichkeiten auseinander und verwendet perfekt modulierte Kräuterrezepturen für eine große Bandbreite von Krankheitsmanifestationen. Daher wird im Folgenden versucht, dieses diagnostische und therapeutische Konzept bei Erkältungskrankheiten systematisch anhand einiger weniger, aber häufig anzutreffender Krankheitsmuster zu erklären. Die Autorin möchte die Leser motivieren, in das chinesische Denken „einzutauchen“, sich mit den TCM-Denkweisen auseinanderzusetzen, um den systematisierbaren Prozess über den Verlauf der Krankheiten zu verstehen und mit unserem heutigen Wissen zu vernetzen. Exzellente Forscher könnten durch Gedankenaustausch und „exzellente Kooperationen“ zusammenarbeiten, um das Problem der Allergie gemeinsam zu bewältigen. Das Thema Allergie ist so komplex, dass es „kompetente Rebellen“ braucht, die den Status quo auf diversen Gebieten kritisch hinterfragen und gleichzeitig sehr hohe Kompetenz in ihrem eigenen Gebiet haben, um neue Lösungsansätze zu finden.


title: Procedures to Investigate Waterborne Illness

text: Humanity could not survive without a reliably clean, safe, and steady flow of drinking water. Since the early 1900s when typhoid fever and cholera were frequently causes of waterborne illness in developed countries, drinking water supplies have been protected and treated to ensure water safety, quality, and quantity. Having access to safe drinking water has always been one of the cornerstones of good public health. Not only safe water is limited to drinking water, but recreational water can also be a source for waterborne illness—both from treated waters such as in swimming pools, whirlpools, or splash pads and from non-treated surface waters such as lakes, rivers, streams and ponds. Recreational waters may cause illness not only from ingestion of pathogens, but also when in contact with eyes, ears, or skin. Some pathogens in water can be acquired by inhalation of aerosols from water that is agitated or sprayed such as in humidifiers, fountains, or misting of produce. This poses a potential risk to those exposed, particularly if they are immunocompromised.


title: Acute Pulmonary Complications of Bone Marrow and Stem Cell Transplantation

text: Recipients of hematopoietic cell transplantation (HCT) are at risk for a variety of acute pulmonary complications including infectious pneumonias and noninfectious acute lung injury syndromes. With advances in HCT technology, prophylaxis and supportive care, overall survival after HCT has improved and the epidemiology of respiratory complications has shifted from early onset to late onset after HCT. However, acute respiratory failure remains the most common indication for admission to an intensive care unit in this population and prognosis is generally poor. Given the broad differential diagnosis of radiographic pulmonary abnormalities in HCT recipients, prompt evaluation with noninvasive testing and invasive diagnostics such as bronchoscopy is warranted. This chapter reviews the current understanding of etiology, diagnostic considerations and treatment of significant acute pulmonary complications in HCT, including idiopathic pneumonia syndrome, cryptogenic organizing pneumonia, and cytomegalovirus pneumonia.


title: Nanotechnology for Detection of Small Mass Difference

text: Mostly, mass of a macroscopic object is determined by comparing the gravitational forces experienced by the object and the body of known mass. Relative uncertainty in 1 kg is pretty small say one part in [Formula: see text]. However, gravitational force of an object of molecular scale is too feeble to detect. Hence, normal method of using a balance will not do for mass measurement on the microscopic scale. Measurement of mass at the microscopic scale is very vital as it serves powerful tool that can provide information about the molecular and atomic composition of an object, detection, prevention and treatment of various diseases.


title: Systemic Risk Basics

text: Attempts to define systemic risk are summarized and found to be deficient in various respects. This introductory chapter, after considering some of the salient features of financial crises in the past, focusses on the key characteristics of banks, their balance sheets and how they are regulated.


title: Immunopathology of the Respiratory System

text: Respiratory immunity is accomplished using multiple mechanisms including structure/anatomy of the respiratory tract, mucosal defense in the form of the mucociliary apparatus, innate immunity using cells and molecules and acquired immunity. There are species differences of the respiratory immune system that influence the response to environmental challenges and pharmaceutical, industrial and agricultural compounds assessed in nonclinical safety testing and hazard identification. These differences influence the interpretation of respiratory system changes after exposure to these challenges and compounds in nonclinical safety assessment and hazard identification and their relevance to humans.


title: Pneumonia After Hematopoietic Stem Cell Transplantation

text: Pneumonia is the main cause of morbidity and mortality after hematopoietic stem cell transplantation. Two thirds of pneumonias observed after both autologous and allogeneic stem cell transplantations are of infectious origin, and coinfections are frequent. One third is due to noninfectious process, such as alveolar hemorrhage, alveolar proteinosis, or alloimmune pulmonary complications such as bronchiolitis obliterans or idiopathic interstitial pneumonitis. Most of these noninfectious complications may require treatment with corticosteroids which may be deleterious in infection. On the other hand, these complications either mimic or may be complicated with infections. Therefore, a precise diagnosis of pneumonia is of crucial importance to decide of the optimal treatment. CT scan is the best procedure for imaging of the lung. Although several indirect biomarkers, such as serum or plasma galactomannan or (1-3) β(beta)-G-glucan, can help in the etiological diagnosis, only direct invasive investigations provide the best chance to identify the cause(s) of pneumonia. Bronchoalveolar lavage (BAL) under fiberoptic bronchoscopy is the procedure of choice to identify the cause of pulmonary infection. It is safe and reproducible, and its diagnostic yield is around 50 % if the BAL fluid is processed at the laboratory according to a prespecified protocol established between the transplanter, the infectious diseases’ specialist, the pneumologist, and the laboratory, allowing the identification of the most likely hypotheses. Transbronchial biopsy does not provide significant additional information to BAL in most cases and more often complicates with bleeding and pneumothorax. In case of a noncontributory BAL, the decision to proceed to a second BAL, a transthoracic biopsy, or a surgical biopsy should be cautiously weighted in a multidisciplinary approach in regard to the benefits and risks of invasive procedures versus empirical treatment.


title: Neurotropic Coronavirus Infections

text: Neurotropic strains of the mouse hepatitis virus (MHV) cause a range of diseases in infected mice ranging from mild encephalitis with clearance of the virus followed by demyelination to rapidly fatal encephalitis. This chapter discusses the structure, life cycle, transmission, and pathology of neurotropic coronaviruses, as well as the immune response to coronavirus infection. Mice infected with neurotropic strains of MHV have provided useful systems in which to study processes of virus- and immune-mediated demyelination and virus clearance and/or persistence in the CNS, and the mechanisms of virus evasion of the immune system.


title: Global Microbial Identifier

text: Human and animal populations are increasingly confronted with emerging and re-emerging infections and often such infections are exchanged between these populations, e.g. through food. A more effective and uniform approach to the prevention of these microbial threats is essential. The technological advances in the next generation sequencing field and decreasing costs of these tests provide novel opportunities in understanding the dynamics of infection—even in real time—through the analysis of microbial genome diversity. The projected significant increase in whole (microbial) genome sequencing (WGS) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source systems. There is therefore an obvious need to develop a global system of whole microbial genome databases to aggregate, share, mine and use microbiological genomic data, to address global public health and clinical challenges, and most importantly to identify and diagnose infectious diseases. The global microbial identifier (GMI) initiative, aims to build a database of whole microbial genome sequencing data linked to relevant metadata, which can be used to identify microorganisms, their communities and the diseases they cause. It would be a platform for storing whole genome sequencing (WGS) data of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require standardization and extensive investments in computational analytical tools. In addition, the wider introduction of WGS in clinical diagnostics can accelerate developments in health care in many poor countries. This overview describes the growing network of stakeholders behind GMI, the contours of the database, and the IT structures needed to serve the GMI user community. It discusses what essentially can be done by a global GMI tool and how the GMI organization could help achieve these goals.


title: Sick Building Syndrome and Other Building-Related Illnesses

text: Sick building syndrome (SBS) and building-related illnesses are omnipresent in modern high-rise buildings. The SBS is a complex spectrum of ill health symptoms, such as mucous membrane irritation, asthma, neurotoxic effects, gastrointestinal disturbance, skin dryness, sensitivity to odours that may appear among occupants in office and public buildings, schools and hospitals. Studies on large office buildings from USA, UK, Sweden, Finland, Japan, Germany, Canada, China, India, Netherlands, Malaysia, Taiwan, and Thailand, substantiate the occurrence of SBS phenomena. The accumulated effects of a multitude of factors, such as the indoor environmental quality, building characteristics, building dampness, and activities of occupants attribute to SBS. A building occupant manifests at least one symptom of SBS, the onset of two or more symptoms at least twice, and rapid resolution of symptoms following moving away from the workstation or building may be defined as having SBS. Based on the peer-reviewed documentation, this chapter elaborates the magnitude of building-related health consequences due to measurable environmental causations, and the size of the population affected. The mechanisms and causative factors of SBS and illnesses include, for example, the oxidative stress resulting from indoor pollutants, VOCs, office work-related stressors, humidification, odours associated with moisture and bioaerosol exposure. Related regulatory standards and strategies for management of SBS and other illnesses are elaborated.


title: Tracheal Infections

text: Infectious processes of the trachea represent a distinct clinical entity with an evolving landscape owing to advances in airway management and vaccination practices. Untreated inflammatory processes of the trachea may present in the form of acute airway obstruction, potentially resulting in significant morbidity and even mortality. Therefore it is important to recognize the cardinal features of some of the common tracheal infectious processes to differentiate them from non-infectious pathology, as the latter is associated with a more indolent course. As with most other infectious processes of the airway, pathogens causing tracheal infection can be bacterial, viral or fungal in nature. Viral etiology represents the most common cause of laryngotracheal infection in a child. Bacterial infections of the trachea are responsible for more significant morbidity, including prolonged hospitalization, need for endotracheal intubation and even an occasional tracheostomy. The current chapter describes the clinical features and microbiology of tracheal infections at large, explores the utility of diagnostic tests, and provides an algorithm for management.


title: Adverse Drug Reactions in the Intensive Care Unit

text: Adverse drug reactions (ADRs) are undesirable effects of medications used in normal doses [1]. ADRs can occur during treatment in an intensive care unit (ICU) or result in ICU admissions. A meta-analysis of 4139 studies suggests the incidence of ADRs among hospitalized patients is 17% [2]. Because of underreporting and misdiagnosis, the incidence of ADRs may be much higher and has been reported to be as high as 36% [3]. Critically ill patients are at especially high risk because of medical complexity, numerous high-alert medications, complex and often challenging drug dosing and medication regimens, and opportunity for error related to the distractions of the ICU environment [4]. Table 1 summarizes the ADRs included in this chapter.


title: Empirical Morphological Model to Evaluate Urban Wind Permeability in High-Density Cities

text: In this chapter, a high-resolution frontal area density (FAD) map that evaluates urban permeability was produced using an empirical model, which takes into account the heterogeneous urban morphology and local wind availability. Using the MM5/CALMET model, the wind data of Hong Kong was simulated, the FAD map of three urban zones were calculated: podium (0–15 m), building (15–60 m), and urban canopy (0–60 m). Wind tunnel test data was used to correlate the FAD understanding of the three zones with pedestrian-level wind environment. Linear regression analysis indicated that a lower urban podium zone yielded the best correlation with the experimental data, and 200 × 200 m was the reasonable resolution for the FAD map. This study further established that the simpler two-dimensional ground coverage ratio (GCR) that is readily available in the planning circle can be used to predict the area’s average pedestrian-level urban ventilation performance of the city. Working with their in-house GIS team using available data, the GCR will provide the planners a way to understand the urban ventilation of the city for decisions related to air paths, urban permeability, and site porosity.


title: Innate Immunity in Viral Encephalitis

text: Innate immune responses to pathogens are evolutionarily ancient and are found in the most primitive organisms. These are highly conserved and are not pathogen-specific, but are in response to classes of molecular structures. Infections can be perceived both extracellularly and intracellularly by Pathogen Associated Molecular Patterns (PAMPs) and their host cell ligands, Pathogen Recognition Receptors (PRRs), among them, Toll-Like Receptors (TLRs). The innate immune response to infection includes the release of soluble preformed mediators, or synthesis of cytoplasmic enzymes, cytokines, chemokines, interferons (IFNs), lipid mediators, proteins of the complement cascade, neurotransmitters, nucleotides, and components of transcription factors (High Mobility Group B1, receptors for sex hormones/steroids). Directed cellular migration of parenchymal astrocytes and microglia, as well as recruitment across the blood brain barrier (BBB) of circulating neutrophils, natural killer, monocytes, macrophages, dendritic cells, and ultimately T lymphocytes to the site of infection are also hallmarks of innate responses to infections. These responding cells contribute their own secreted effector molecules and effector activities (such as phagocytosis). Distinct viruses are capable of infecting every cell type (endothelial cells, ependymal cells, perivascular macrophages and pericytes, astrocytes, microglia, oligodendrocytes, Schwann cells, and neurons) in the central nervous system (CNS). These CNS infections challenge the host with a different set of problems than do peripheral viral infections. Among the complications are (a) neurons that rarely express Class I or Class II Major Histocompatibility Complex (MHC) molecules and are thus not suitable targets for either CD4(+) or CD8(+) MHC-restricted T cells, (b) an enclosed volume that is constrained from swelling during inflammation, as well as poorly developed lymphatic drainage, and (c) the immunologic privilege of the CNS which leads to extremely limited immune surveillance for pathogens. Therefore, the role of innate immunity, both from CNS-resident cells and their products, and from circulating inflammatory cells and molecules which traverse the BBB are essential to “buy time,” inhibiting viral replication and dissemination, until the host can marshal an adaptive immune response. The immune responses are crucial for host survival from the infection. Consequently, successful pathogens, especially those that persist, have developed a wide variety of evasive approaches to limit the inhibition of replication. Many of these pathways are highlighted in individual chapters that precede this one. These evasive measures range from neutralizing host secreted molecules (cytokines and chemokines) with soluble receptors, encoding anti-inflammatory proteins in their genome, preventing signal transduction, blocking inhibition of protein synthesis, degradation of essential antiviral molecules, preventing apoptosis, and blockade of the nuclear pore complex. In this chapter, I will attempt to cover the breadth of the innate immune response to viral infection, but will also devote more space to generally under-considered aspects than to the well-known components. There are some caveats to consider, as most experiments have been performed in the murine model and not in man; further, conclusions from experiments using in vitro cultured cells (whether primary or established lines) may not reflect physiological conditions in an undisturbed CNS. Lastly, we now appreciate the complexities imposed on hosts by polymorphisms in genes of critical pathways, leading to increased susceptibility or resistance of that individual but not others.


title: Coda: Transformative Encounters: Desiring Aliens and Hospitality in District 9

text: This final chapter considers Neill Blomkamp’s film District 9 for its commentary on human and non-human alien relationships. Returning to many of the issues raised in the previous chapters, this coda analyzes the overt biopolitical dimensions of the film and considers how desire works to challenge the violent machinations of the multinational security company, Multi-National United. It examines how the film’s protagonist gets caught up in logics of exclusion in his experience of becoming-alien and approaches a position of bare life, outside the protections of the community. Ultimately, the chapter concludes the project by arguing that new, creative modes of resisting neocolonial and capitalist violence will be needed in response to biopolitical regimes, and that such creativity might arise from different desires and other modes of affect.


title: China in the Fight Against the Ebola Crisis: Human Security Perspectives

text: The outbreak of the Ebola virus disease (EVD) in West Africa became one of the worst disease-driven humanitarian crises in modern history. The crisis turned the global securitization of health issues into unprecedented levels, at the same time, aligned closely with human security frameworks and thus has significant impacts on national foreign and aid policies. China has played a significant role in the global fight against Ebola, indicating important changes in its foreign policy orientations. Based on the lessons drawn from China’s operation in Africa, it is argued that states must transcend their narrow national interest and seriously consider the dignity and well-being of vulnerable people.


title: Monoclonal Antibodies Approved for Cancer Therapy

text: Twenty-four monoclonal antibodies (mAbs) targeted to a total of 16 different antigens are currently approved for the treatment of an increasing number of cancers. Six are directed against antigens expressed on B lymphocytes (ibritumomab tiuxetan, obinutuzumab, ofatumumab, and rituximab to CD20, brentuximab vedotin to CD30, and alemtuzumab to CD52); cetuximab, panitumumab, and necitumumab target EGFR; bevacizumab and ramucirumab are specific for VEGF and VEGFR2, respectively; pertuzumab, trastuzumab, and ado-trastuzumab target HER2; nivolumab and pembrolizumab are directed to the programmed cell death protein 1 (PD-1); and denosumab, ipilimumab, siltuximab, and dinutuximab recognize RANKL, CTLA-4, IL-6, and the disialoganglioside (GD2), respectively. In November 2015, the FDA approved daratumumab, the first anti-CD38 mAb and the first mAb to be approved for the treatment of multiple myeloma. Elotuzumab, targeted to the receptor SLAMF7, was also given approval for multiple myeloma soon after. Two antibodies are bispecific: the rat-mouse chimera, catumaxomab, recognizes both EpCAM and CD3, while blinatumomab, a bispecific T-cell-engaging (BiTE) fusion protein, targets both CD19 and CD3. Although mAbs used for cancer immunotherapy are generally better tolerated than small molecule chemotherapeutic drugs, their range of adverse effects is still wide and varied from mild gastrointestinal symptoms and transient rashes to severe cytopenias; anaphylaxis; autoimmunity; pulmonary, cardiac, hepatic, kidney, neurological, and embryofetal toxicities; and rare life-threatening toxidermias. Because of their immunogenic potential, mAbs generally carry warnings of immune reactions, especially anaphylaxis, but the observed incidences of such reactions are actually quite small. Cytopenias occur in some patients treated with mAbs during anticancer immunotherapy, but the underlying mechanisms frequently remain unexplored. Type II and III hypersensitivities induced by mAbs may be underdiagnosed. Severe infusion reactions have been reported for all the mAbs although some show a much higher incidence with the chimeric rituximab and humanized trastuzumab antibodies being the leading offenders. Distinguishing features in the literature between cytokine release syndrome and severe infusion reactions are often not clear. At least ten of the currently approved mAbs for cancer therapy show some pulmonary toxicity. These pulmonary adverse events can be grouped into four categories: interstitial pneumonitis and fibrosis, acute respiratory distress syndrome (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP), and hypersensitivity pneumonitis. Cardiac adverse events, including congestive heart failure, decreased LVEF, myocardial infarction, cardiac arrest, and arrhythmias, have occurred with at least 11 of the mAbs. Papulopustular eruptions, cutaneous reactions that are not immune-mediated, as well as a range of other adverse mucocutaneous effects, are elicited in a large proportion of patients by mAbs targeted to EGFR. Other rare but mAb-induced serious adverse events are tumor lysis syndrome and progressive multifocal leukoencephalopathy.


title: Henipaviruses

text: The first henipaviruses, Hendra virus (HeV), and Nipah virus (NiV) were pathogenic zoonoses that emerged in the mid to late 1990s causing serious disease outbreaks in livestock and humans. HeV was recognized in Australia 1994 in horses exhibiting respiratory disease along with a human case fatality, and then NiV was identified during a large outbreak of human cases of encephalitis with high mortality in Malaysia and Singapore in 1998–1999 along with respiratory disease in pigs which served as amplifying hosts. The recently identified third henipavirus isolate, Cedar virus (CedPV), is not pathogenic in animals susceptible to HeV and NiV disease. Molecular detection of additional henipavirus species has been reported but no additional isolates of virus have been reported. Central pathological features of both HeV and NiV infection in humans and several susceptible animal species is a severe systemic and often fatal neurologic and/or respiratory disease. In people, both viruses can also manifest relapsed encephalitis following recovery from an acute infection, particularly NiV. The recognized natural reservoir hosts of HeV, NiV, and CedPV are pteropid bats, which do not show clinical illness when infected. With spillovers of HeV continuing to occur in Australia and NiV in Bangladesh and India, these henipaviruses continue to be important transboundary biological threats. NiV in particular possesses several features that highlight a pandemic potential, such as its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals along with a capacity of limited human-to-human transmission. Several henipavirus animal challenge models have been developed which has aided in understanding HeV and NiV pathogenesis as well as how they invade the central nervous system, and successful active and passive immunization strategies against HeV and NiV have been reported which target the viral envelope glycoproteins.


title: Acute Respiratory Failure

text: Acute respiratory failure accounts for 25–40 % of ICU admissions and carries a mortality rate of 30 % or more. In this chapter, we classify acute respiratory failure in two main types, based on their primary physiologic abnormality: Disorders of the airways, where increase of airway resistance to gas flow determines pharmacologic treatment and ventilatory strategies. These disorders are mainly asthma and chronic obstructive pulmonary disease. Disorders of the alveoli, where a decrease of lung compliance mandates the use of higher ventilatory pressures that can recruit but also damage the lung. These disorders include the acute respiratory distress syndrome, pneumonia, acute cardiogenic pulmonary edema, and influenza. Additional types of acute respiratory failure are described elsewhere in this book: disorders that result from neuromuscular disease in Chap. 10.1007/978-3-319-19668-8_19 and pulmonary disorders of the circulation, including pulmonary thromboembolism, in Chap. 10.1007/978-3-319-19668-8_27. Finally, we provide a section on weaning from mechanical ventilation, which includes the pathophysiology of the ventilatory load imposed by the prolonged acute respiratory failure, the possible ways to support the weakened respiratory system, and the current process of screening and testing for readiness to remove the ventilator.


title: On Health and Water Security

text: Climate change is severely affecting the availability of water and its quality. Therefore it represents a direct challenge to health. Not only the water-born, but also the vector and temperature-related diseases are challenging the existing health system and safe water supply. Thus, water and health security have progressively been challenged primarily by pollution, waste, toxins and climate-change-related hazards and disasters.


title: Pathophysiology of Portal Hypertension

text: The bases of our current knowledge on the physiology of the hepatic portal system are largely owed to the work of three pioneering vascular researchers from the sixteenth and the seventeenth centuries: A. Vesalius, W. Harvey, and F. Glisson. Vesalius is referred to as the founder of modern human anatomy, and in his influential book, De humani corporis fabrica libri septem, he elaborated the first anatomical atlas of the hepatic portal venous system (Vesalius 2013). Sir William Harvey laid the foundations of modern cardiovascular research with his Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (Harvey 1931) in which he established the nature of blood circulation. Finally, F. Glisson characterized the gastrointestinal-hepatic vascular system (Child 1955). These physiological descriptions were later complemented with clinical observations. In the eighteenth and nineteenth centuries, Morgagni, Puckelt, Cruveilhier, and Osler were the first to make the connection between common hepatic complications – ascites, splenomegaly, and gastrointestinal bleeding – and obstruction of the portal system (Sandblom 1993). These were the foundations that allowed Gilbert, Villaret, and Thompson to establish an early definition of portal hypertension at the beginning of the twentieth century. In this period, Thompson performed the first direct measurement of portal pressure by laparotomy in some patients (Gilbert and Villaret 1906; Thompson et al. 1937). Considering all these milestones, and paraphrasing Sir Isaac Newton, if hepatologists have seen further, it is by standing on the shoulders of giants. Nowadays, our understanding of the pathogenesis of portal hypertension has largely improved thanks to the progress in preclinical and clinical research. However, this field is ever-changing and hepatologists are continually identifying novel pathological mechanisms and developing new therapeutic strategies for this clinical condition. Hence, the aim of this chapter is to summarize the current knowledge about this clinical condition.


title: Intraoperativer Volumenersatz, Transfusion und Behandlung von Gerinnungsstörungen

text: Sowohl der operative Eingriff als auch die Narkose führen zu Veränderungen des intravasalen Volumenstatus des Patienten. Ziele der perioperativen Flüssigkeits- bzw. Volumentherapie sind die Aufrechterhaltung des zirkulierenden intravasalen Volumen (Normovolämie), einer adäquaten Gewebeperfusion und -oxygenierung, des Gleichgewichts im Elektrolythaushalt sowie die Aufrechterhaltung der Normoglykämie.


title: Clinical Use of DNA Vaccines

text: Owing to their unique advantages in simplicity, safety, scalability, and possibility of repeated administrations, DNA vaccines represent an appealing and competitive immunization approach for a wide array of conditions, including but not limited to infectious diseases and cancer immunotherapy. Despite the exciting efficacy observed in preclinical studies, DNA vaccines have faced challenges in inducing strong immune responses in humans. This unexpected poor immunogenicity has severely hampered the translation of DNA vaccines from investigational medications to licensed products. To overcome this obstacle, tremendous efforts have been made to improve antigen expression and enhance immunogenicity. Among these endeavors, in vivo DNA electroporation (EP) has proved to be a breakthrough technology capable of mediating efficient DNA uptake and resulting in enhanced antigen expression and vaccine immunogenicity. EP-mediated DNA delivery has become one of the major platforms used in clinical trials to evaluate DNA vaccines in humans. In this chapter, in addition to EP delivery, other progress made in DNA vaccine development including plasmid optimization, antigen design, and immunologic adjuvants is also reviewed. Finally, the use of DNA vaccines in the context of clinical trials for infectious diseases and cancer immunotherapy is summarized. Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. Based on the advantages of DNA vaccines and the immense progress, led by the electroporation-mediated vaccine delivery, DNA vaccines appear to have the potential to fundamentally transform the vaccine field, providing important benefits for preventing and curing diseases.


title: Lung Transplantation

text: The therapeutic options for patients with advanced pulmonary parenchymal or vascular disorders are currently limited. Lung transplantation remains one of the few viable interventions, but on account of the insufficient donor pool only a minority of these patients actually undergo the procedure each year. Following transplantation there are a number of early and late allograft complications such as primary graft dysfunction, allograft rejection, infection, post-transplant lymphoproliferative disorder and late injury that is now classified as chronic lung allograft dysfunction. The pathologist plays an essential role in the diagnosis and classification of these myriad complications. Although the transplant procedures are performed in selected centers patients typically return to their local centers. When complications arise it is often the responsibility of the local pathologist to evaluate specimens. Therefore familiarity with the pathology of lung transplantation is important.


title: Contextualisation on Gender, Peace, Security and Environment

text: These texts on gender, peace, security and environmental problems were written based on my concern about an unequal and unsustainable development process during the past six decades, when the history of the earth moved from the Holocene to the Anthropocene (Crutzen in Nature 415(6867):23, 2002). The following chapters were influenced by theoretical reflections, my life experience and my scientific training on three continents, at the universities of Antananarivo (Madagascar), Paris (France), Zürich (Switzerland) and in Mexico ( CISINAH, UAM and UNAM). The influence of these three cultures with very different historical backgrounds explains my progressively broadened understanding of the global development process. The post-colonial experiences in Africa in the 1960s, the violence left behind by the former colonial powers, and the outcome of civil wars, corruption and destruction of irreplaceable ecosystems and species forced me to understand not only the physical functioning of the human body (medicine), but also its psychological behaviour that supports or obstructs a healthy human life (psychology) and avoids environmental destruction ( ecology). My understanding of the links between the human body, the mind and the environment (anthropology) resulted first in an intuitive and later an interdisciplinary approach to these four interrelated circles (body, mind, environment and human relations). Understanding the importance of these four study subjects triggered in me a commitment to responsible scientific and sustainable behaviour towards other human beings, but also to nature.


Optimizing the use of Upper GI Endoscopy after Laparoscopic Roux-en-Y Gastric Bypass


title: What Are We Talking About?

text: In this chapter, we present a few definitions of post-truth and explain why the human capacity for lying and influencing others with false information, which is not new in human history, has given birth to alarming new dangers in recent years. We also set forth our path for describing the history and theoretical claims underlying the phenomenon of post-truth, accounting briefly for the social, political, and economic changes posed by individualization, bureaucratization, and globalization issues that will not be addressed in the remainder of the book.


title: Hematologic neoplasms: Interpreting lung findings in chest computed tomography()

text: Lung disease is very common in patients with hematologic neoplasms and varies in function of the underlying disease and its treatment. Lung involvement is associated with high morbidity and mortality, so it requires early appropriate treatment. Chest computed tomography (CT) and the analysis of biologic specimens are the first line diagnostic tools in these patients, and sometimes invasive methods are necessary. Interpreting the images requires an analysis of the clinical context, which is often complex. Starting from the knowledge about the differential diagnosis of lung findings that radiologists acquire during training, this article aims to explain the key clinical and radiological aspects that make it possible to orient the diagnosis correctly and to understand the current role of CT in the treatment strategy for this group of patients.


title: Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years()

text: OBJECTIVES: To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. METHODS: This was a cross‐sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. RESULTS: HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co‐detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV‐infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p = 0.006), but had more comorbidities (40% and 27%, respectively; p = 0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r = −0.636, p < 0.001) but no correlation with rainfall (r = −0.036, p = 0.866). CONCLUSION: HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co‐detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons.


title: Emerging and Re-emerging Infectious Diseases

text: Emerging infectious diseases (EIDs) are characterized by a new or an increased occurrence within the last few decades. They include the following categories Emerging diagnosis of infectious diseases: old diseases that are newly classified as infectious diseases because of the discovery of a responsible infectious agent.


title: Genome

text: Canis lupus familiaris, der Haushund, wurde vor rund 15.000 Jahren von den Menschen domestiziert. Obwohl es viele verschiedene Varianten von Wölfen gibt, ähneln sich diese ziemlich stark, doch das trifft auf den „besten Freund des Menschen“ nicht zu. Die Fédération Cynologique Internationale (FCI), weltweit größter Dachverband der Hundezüchter, erkennt über 300 Hunderassen an. Genetiker gehen von rund 100 echten Hunderassen aus, der Rest seien Varietäten. Hunderassen sehen nicht nur recht unterschiedlich aus, sondern sie unterscheiden sich auch stark in ihrer Körpergröße. So wiegt beispielsweise ein durchschnittlicher Chihuahua nur 1,5 kg, während ein Schottischer Jagdhund 70 kg auf die Waage bringt. Kein anderes Säugetier zeigt eine so starke phänotypische Variabilität. Außerdem gibt es Hunderte von genetisch bedingten Krankheiten bei Hunden, und für viele davon findet sich auch ein Gegenstück bei Menschen. Das Hundegenomprojekt begann in den späten 1990er-Jahren, um herauszufinden, welche Gene für die genetische Variabilität verantwortlich sind und welche Zusammenhänge zwischen Genen und Krankheiten bestehen.


title: Evolution von Genen und Genomen

text: Der Erste Weltkrieg endete im November 1918. Die Zahl der Todesfälle in den vier Kriegsjahren wurde jedoch schon bald übertroffen von den Opfern einer massiven Grippeepidemie, an der weltweit über 50 Mio. Menschen starben – und damit mehr als doppelt so viele wie in den Schlachten des Ersten Weltkriegs. Die Pandemie von 1918/1919 war insofern bemerkenswert, als die Sterberate unter jungen Erwachsenen, die einer Grippe gewöhnlich mit viel geringerer Wahrscheinlichkeit zum Opfer fallen als Kinder und Greise, um das 20-Fache höher lag als bei den vorherigen und später folgenden Grippeepidemien. Warum erwies sich dieses Grippevirus speziell unter den normalerweise widerstandsfähigsten Menschen als so tödlich? Der Virusstamm von 1918 löste im menschlichen Immunsystem eine besonders starke Reaktion aus. Infolge dieser Überreaktion waren Menschen mit einem leistungsfähigen Immunsystem tendenziell stärker betroffen.


title: Micro-organismen en infectieziekten bij de mens: algemene principes

text: Infectieziekten zijn te beschouwen als een aparte groep ziekten van de mens. Steeds gaat het om ziekten die het gevolg zijn van een interactie tussen de mens en een ander biologisch agens: een micro-organisme. Bij een infectieziekte is er sprake van een bepaalde vorm van interactie waarbij schade optreedt voor de mens. Verreweg de meeste interacties tussen mensen en micro-organismen zijn echter niet schadelijk voor de mens. Infectieziekten behoren tot de meest prevalente aandoeningen van de mens en op mondiaal niveau zijn ze nog steeds de belangrijkste oorzaak van vermijdbare sterfte. Daarom is het voor het onderwijs in de geneeskunde van groot belang infectieziekten te beschouwen als een aparte groep ziekten, met een unieke etiologie, epidemiologie, pathogenese, diagnostiek, behandeling en preventie. Infecties komen op alle leeftijden voor en kunnen alle organen en weefsels van het lichaam treffen. Infectieziekten zijn daardoor een belangrijk paradigma in de geneeskunde. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_1) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers.


title: Supportive Care in Hematology

text: Patients with hematological malignancies such as leukemias and lymphomas are predisposed to a wide spectrum of infections that need special attention. These patients are immunosuppressed not only as a result of the immune defects associated with the underlying disease, but also because of the treatment regimens that generally further decrease the patient’s resistance to infections. An intensive transfusion support with platelets, red cell concentrates, immunoglobulins, cytokines, and other drugs is necessary. Many patients also need antiemetic agents, nutritional support, pain medication, and, very often, venous catheters. All of these measures are considered supportive care and apply in a similar fashion to the high-dose treatment of solid tumors. Supportive care measures, along with the treatment and prophylaxis of infections, are discussed in this chapter. Transfusion support is discussed in Chapter 22.


Verleihung des BWK Umweltpreises NRW 2020 an das Projekt "Schüler bauen für Haiti"


BWK INTERN


title: Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

text: The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an “inventory” of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered.


Gedanken zur Corona-Krise


title: Development and use of the H strain of avian infectious bronchitis virus from the Netherlands as a vaccine: a review

text: The H strain of infectious bronchitis (IB) was one of the earliest live attenuated IB vaccines to be developed and has continued to be used in most parts of the world for almost 50 years. It was developed for use at both the 52nd (H52) and 120th (H120) vaccine levels and, because of it ability to provide heterologous cross-protection against a number of IB viruses of different serotypes, has proved to be one of the most enduring live attenuated IB vaccines. In fact, the H120 vaccine is possibly the most widely used live attenuated IB vaccine globally to this day. The use of H52 has, however, declined with the introduction of safe and highly efficacious inactivated IB vaccines. This review documents the original studies to isolate and attenuate the H strain by serial embryo passage, and describes the early studies to demonstrate its efficacy in laboratory studies and under field conditions. The efficacy of the H vaccine in providing cross-protection against some of the many IB variants now reported worldwide is also discussed, and possible future vaccination strategies for IB considered.


title: A new genotype of nephropathogenic infectious bronchitis virus circulating in vaccinated and non-vaccinated flocks in China

text: Five strains of infectious bronchitis virus (IBV) were isolated from five layer flocks that had nephropathogenic infection in four provinces in China. Among them, three of the five flocks had been vaccinated against infectious bronchitis. Virulence studies indicated that the five Chinese IBV isolates caused 10 to 30% mortality in 15-day-old specific pathogen free chickens and gross lesions were mainly confined to the kidneys in all of the dead chickens. Two oligonucleotide pairs, S1Uni2 and S1Oligo3′ or S1Oligo5′ and S1Oligo3′, were used after propagation of the isolates in embryonated eggs to amplify the S1 protein genes of the spike protein. The cDNA derived by reverse transcriptase-polymerase chain reaction was cloned and sequenced. The nucleotide and amino acid sequence of S1 protein gene had a similar degree of identity (≥92%) among the five Chinese IBV isolates. The nucleotide and amino acid identity of the S1 protein gene between the five Chinese IBV isolates and 16 strains of other IBVs varied from 60 to 81%. This clearly showed that the five Chinese IBV isolates comprised a separate genotype. These results demonstrated, for the first time, that there is a new genotype of nephropathogenic IBV circulating in vaccinated and non-vaccinated flocks in China.


title: Molecular epizootiology of infectious bronchitis virus in Sweden indicating the involvement of a vaccine strain

text: To improve the detection and molecular identification of infectious bronchitis virus (avian coronavirus), two reverse transcriptase-polymerase chain reaction (PCR) assays were developed. As ‘diagnostic PCR’, a set of consensus nested primers was selected from highly conserved stretches of the nucleocapsid (N) gene. As ‘phylogeny’ PCR, a fragment of the spike protein gene (S1) was amplified and the PCR products were directly sequenced. To study the phylogenetic relationships of the viruses from various outbreaks, studies of molecular epizootiology were performed in Sweden, a Nordic region, where the occurrence of natural cases of the disease is relatively low and the occasional use of live vaccine(s) is well recorded and monitored. The disease appeared in the region in 1994, associated with production problems among layers of various ages. During outbreaks in 1995 and 1997, both layers and broilers were affected. To reduce losses, a live attenuated vaccine has been applied since 1997. By examining 12 cases between 1994 and 1998, molecular epizootiology revealed that, before 1997, the viruses had gene sequences very similar to strains of the Massachusetts serotype. However, comparative sequence analysis of the S1 gene revealed that the identity was not 100% to any of the strains of this serotype that we analysed. A virus related to the Dutch-type strain, D274, was also identified on one farm. Surprisingly, from 1997, the year that vaccination commenced with a live Massachusetts serotype vaccine, the majority of viruses detected had S1 sequences identical to the live Massachusetts vaccine strain. This genetic relation to the vaccine virus was also confirmed by N gene sequence analysis. The studies of molecular epizootiology reveal a strong probability that the vaccination had lead to the spread of the vaccine virus, causing various disease manifestations and a confusing epizootiological situation in the poultry population.


title: Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus

text: Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopavo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, Severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract—the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils, rectum and cloaca, usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks may not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced αβ T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.


title: Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture

text: The avian coronavirus infectious bronchitis virus (IBV) is a major economic pathogen of domestic poultry that, despite vaccination, causes mortality and significant losses in production. During replication of the RNA genome there is a high frequency of mutation and recombination, which has given rise to many strains of IBV and results in the potential for new and emerging strains. Currently the live-attenuated vaccine gives poor cross-strain immunity. Effective antiviral agents may therefore be advantageous in the treatment of IBV. Lithium chloride (LiCl) is a potent inhibitor of the DNA virus herpes simplex virus but not RNA viruses. The effect of LiCl on the replication of IBV was examined in cell culture using two model cell types; Vero cells, an African Green monkey kidney-derived epithelial cell line; and DF-1 cells, an immortalized chicken embryo fibroblast cell line. When treated with a range of LiCl concentrations, IBV RNA and protein levels and viral progeny production were reduced in a dose-dependent manner in both cell types, and the data indicated that inhibition was a cellular rather than a virucidal effect. Host cell protein synthesis still took place in LiCl-treated cells and the level of a standard cellular housekeeping protein remained unchanged, indicating that the effect of LiCl was specifically against IBV.


Irene Higginson: progress towards a better ending


title: Community‐acquired pneumonia among children: the latest evidence for an updated management()

text: OBJECTIVE: To provide cutting‐edge information for the management of community‐acquired pneumonia in children under 5 years, based on the latest evidence published in the literature. DATA SOURCE: A comprehensive search was conducted in PubMed, by using the expressions: “community‐acquired pneumonia” AND “child” AND “etiology” OR “diagnosis” OR “severity” OR “antibiotic”. All articles retrieved had the title and the abstract read, when the papers reporting the latest evidence on each subject were identified and downloaded for complete reading. DATA SYNTHESIS: In the era of largely implemented bacterial conjugate vaccines and widespread use of amplification nucleic acid techniques, respiratory viruses have been identified as the most frequent causative agents of community‐acquired pneumonia in patients under 5 years. Hypoxemia (oxygen saturation ≤ 96%) and increased work of breathing are signs most associated with community‐acquired pneumonia. Wheezing detected on physical examination independently predicts viral infection and the negative predictive value (95% confidence interval) of normal chest X‐ray and serum procalcitonin < 0.25 ng/dL was 92% (77‐98%) and 93% (90‐99%), respectively. Inability to drink/feed, vomiting everything, convulsions, lower chest indrawing, central cyanosis, lethargy, nasal flaring, grunting, head nodding, and oxygen saturation < 90% are predictors of death and can be used as indicators for hospitalization. Moderate/large pleural effusions and multilobar infiltrates are predictors of severe disease. Orally administered amoxicillin is the first line outpatient treatment, while ampicillin, aqueous penicillin G, or amoxicillin (initiated initially by intravenous route) are the first line options to treat inpatients. CONCLUSIONS: Distinct aspects of childhood community‐acquired pneumonia have changed during the last three decades.


Corona


title: Außerklinische Beatmung: Lungenerkrankungen

text: In den letzten Jahren ist eine deutliche und kontinuierliche Zunahme von meist schwerkranken Patienten zu konstatieren, die außerhalb einer Klinik beatmet werden. Diese Patienten stellen eine wachsende Herausforderung für alle an der Versorgung Beteiligten dar. In der Regel erfolgt die ärztliche Weiterbetreuung und die Verordnung der benötigten Hilfsmittel durch Hausärzte. In diesem Beitrag lesen Sie, was ein Hausarzt aus dem Bereich der Beatmungsmedizin wissen sollte.


Hausarztleben im Bann des Coronavirus: Mehrarbeit und Anerkennung


The Nature and Classification of Animal Viruses


Research Forum Educational Program 2007


title: Electron microscopy

text: This chapter provides a detailed methodology of some of the basic electron microscopic (EM) techniques currently used in virology. The chapter is subdivided into four sections: a general introduction, negative staining procedures, thin sectioning procedures, and briefly scanning EM. Following a brief discussion of the principles, each technique is given in the chapter in sufficient detail to be followed as a recipe. Modifications are included within the methodology. The size, equipment, and organization of an EM unit naturally vary according to the service requirements. There are some basic requirements that need to be considered. Immune electron microscopy is the visualization of the reaction between an antigen, usually a virus, and an antibody and is used to detect either component of this reaction. Thus, the technique has been used to detect serological responses to such viruses as Norwalk virus. The technique has assisted in the identification of rubella virus and been diagnostically used to identify Hepatitis B virus infection and viruses associated with diarrhea.


Practical epidemiology of poultry disease and multifactorial conditions


Protein A–Gold: Nonspecific Binding and Cross-Contamination


title: Testing of Adenoviral Vector Gene Transfer Products: FDA Expectations

text: This chapter describes the agency requirements and guidelines for drug development of adenoviral-containing products. The Food and Drug Administration (FDA) assessment of safety and ultimately effectiveness of adenovirus containing products involves thorough evaluation of the information contained in the Investigational New Drug Application (IND), and any supporting information cross-referenced to another IND or drug master file. Many factors contribute to development of FDA recommendations and requirements for characterization of adenovirus vectors. The FDA receives input and feedback from a variety of sources in formulating recommendations regarding adenovirus manufacturing and characterization. The recommendations may change with advances in technology and through accumulating experience. FDA considers the potential risks and benefits of each vector product and each proposed clinical trial when making its recommendations. The FDA is cognizant of the need for flexibility in its recommendations and will consider many factors, including the intended target population, the seriousness of the disease under study, the potential benefits and risks from the investigational product, when advising sponsors about their adenovirus development program.


Endomembrane System of Plants and Fungi


The pyrexic cat


Vaccines and vaccination


Mannosidases in Mammalian Glycoprotein Processing


title: Lactate Dehydrogenase-Elevating Virus

text: Lactate dehydrogenase-elevating virus (LDV) is a mouse arterivirus, unusual in its extreme host specificity and its persistence in the circulation of the infected host that naturally infects wild mice. Although, probably not as frequent in laboratory mouse colonies as it used to be, LDV infection may affect experimental results, primarily through its effects on the host immune responses. On the other hand, because of its unique properties, LDV infections serve as a good animal model for viral persistence, virally induced immunomodulation, and pathogenic infection of neurons in the central nervous system. However, the inability of LDV to infect in transformed cell lines and to cause a detectable cytopathic effect in cell cultures in which it replicates, such as mouse peritoneal exudate cells, represents technical obstacles to the further analysis of this virus. Identification of the cell receptor utilized by LDV would constitute a major advance, since this might lead to the creation of a cell line permissive to LDV infection. Whereas LDV is a natural and sometimes pathogenic infectious agent of the mouse, it does not currently represent a major threat to animal facilities. The virus is not very contagious and there are a number of easy methods available to detect infected mice. Moreover, further study of the interaction between relatively silent viruses, such as LDV, and their host species should lead to new insights into the mechanisms by which viruses can establish and maintain relatively harmless, persistent infections in their hosts.


Infectious Disorders of the Liver


Neonatology


Foal Diarrhea


Prevention and Treatment of Viral Diseases


The cat with signs of acute small bowel diarrhea


title: Travel

text: Travel changes people and places. The traveler can be the target and sufferer from microbial threats; the traveler can also provide the microbial transport system. Traveling humans alter infectious diseases patterns by introducing pathogenic microbes or resistance, or virulence factors into new populations. The movement of pathogenic microbes through history has been intimately linked to the capacity of humans to travel and to migrate to new locations. Today, humans have the capacity to reach virtually any city in the world within a day or two. Travel to tropical and developing countries are increasing more rapidly than travel to developed countries, and all projections suggest that human travel will continue to increase in the foreseeable future. Infectious diseases influence decisions about travel and trade; and travelers change the epidemiology of infectious diseases. Travel has played an essential role in the movement of HIV/AIDS throughout the world. Rapid international air travel moved the virus that causes SARS to multiple countries within weeks. Travel has been and will continue to be important in the movement of human influenza. Travel consists of sequential shared environments, often with people from diverse regions of the world. It should be considered a loop, and not just an origin and destination. Travel has created extensively interconnected world in terms of microbial threats.


Cultivation, Assay, and Analysis of Viruses


Peritoneum and retroperitoneum


title: Mouse Hepatitis Virus

text: This chapter attempts to provide an overview of the important aspects of mouse hepatitis virus (MHV) experimental biology while emphasizing the virus as a naturally occurring mouse pathogen. Even this is complicated, as it is impossible to generalize with this virus, due to marked differences in the biologic behavior of the myriad virus strains, plus the marked effects of a large number of host factors. It is now known that the MHV group is represented by numerous variants that are constantly mutating, and that these viruses can be biologically separated into respiratory (polytropic) MHVs and enterotropic MHVs, with distinctly different patterns of tissue tropism. This dichotomy is emphasized for discussion, but biology is never absolute. Many of the early MHV isolations are made as a result of contamination of biological materials that correlated with their polytropic biologic behavior. Their stated tropisms frequently were the result of the investigators' research interests and many have therefore been subjected to selective passage that favors a particular tissue tropism. All MHV isolates are related genetically and antigenically, but isolates can be differentiated by genetic sequencing, cross-serum neutralization, or with monoclonal antibodies. Genetic and antigenic relationships are not predictive of biologic behavior.


Neonatal necrotizing enterocolitis


OVERVIEW OF THE STATE OF THE ART IN HEALTH MONITORING


Ferret gastrointestinal and hepatic diseases