title: Neurologie

text: Obwohl die neurologische Intensivmedizin eine eigene Disziplin darstellt, finden sich auf allen Intensivstationen neurologische Erkrankungen und Syndrome, insbesondere im Sinne fachübergreifender Komplikationen. Altersbedingt ist in den nächsten Jahren mit einer Zunahme neurologischer Erkrankungen zu rechnen, besonders von Schlaganfällen, sowohl ischämischen als auch intrazerebralen Blutungen und epileptischen Anfällen inkl. Status epilepticus. Gerade bei internistischen Patienten finden sich gelegentlich eine bakterielle oder virale Meningitis/Enzephalitis, oft im Sinne einer zerebralen Mitbeteiligung. Häufige neurologische Syndrome auf Intensivstationen sind unklare Bewusstlosigkeit, Critical-illness-Neuropathie/Myopathie und anoxischer Hirnschaden sowie der irreversible Hirnfunktionsausfall. Seltenere Krankheitsbilder wie das Guillain-Barré-Syndrom sollten allen Intensivmedizinern bekannt sein, um eine fachspezifisch neurologische Weiterbehandlung zu gewährleisten.


title: Surfactant

text: Exogenous pulmonary surfactant, widely used in neonatal care, is one of the best-studied treatments in neonatology, and its introduction in the 1990s led to a significant improvement in neonatal outcomes in preterm infants, including a decrease in mortality. This chapter provides an overview of surfactant composition and function in health and disease and summarizes the evidence for its clinical use.


title: Gastroenterologie

text: Das Kapitel enthält Angaben zum Management und der Therapie gastroenterologischer Notfälle, nämlich akutes Abdomen, akute obere und untere gastrointestinale Blutung, Ösophagustraumen und -verätzungen, akute Enterokolitis, akute Pankreatitis sowie Komplikationen und akute Erkrankungen der Gallenwege und der Leber. Abgerundet wird das Kapitel durch eine umfangreiche Darstellung der Abdomensonographie auf einer Intensivstation.


title: Pros and cons of the application of evolutionary theories to the evolution of SARS-CoV-2

text: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe damage to the world. With the support of classic evolutionary theories and population genetics principles, many studies on the origin of SARS-CoV-2 have revealed encouraging results but meanwhile some are still under debate. We are concerned with the validity of applying classic evolutionary theories and formula to the evolution of RNA viruses. We have raised several confounding factors like the RNA replication feature and the RNA modification systems of the hosts, which might jeopardize the validity of the application of classic methods to analyze the SARS-CoV-2 data.


Terugblik aidstijdperk 1981-1996


Het post-coronatijdperk


nieuws: Berichten uit de verpleegkundige praktijk


Omslagpunt


van waardering kun je geen wc-papier kopen


title: Examples of Risk Information Concealment Practice

text: The Vajont hydropower station dam and reservoir was located at the foot of Mt. Toc in the Dolomite region of the Italian Alps. In October 1963, a large landslide of 260 million m(3) of rock (equivalent of cube with a 650 meter side) filled the reservoir of the dam, initiating a 150–250 m high wave, which overtopped the dam and wiped out several villages in the nearby Piave valley, resulting in the death of at least 1921 people.


title: Catastrophic disturbance and vegetation on Little Slope, Lord Howe Island

text: Little Slope is a series of debris avalanche deposits below basalt cliffs 700 m high at the southern end of Lord Howe Island (31°35′S 159°05′E). There are five distinct physiographic areas on the slope, each separated by sharp boundaries which mostly correspond to boundaries between features on the cliffs above. The physiography is a consequence of a series of landslides of different, but unknown, ages. A model of the physiographic history is presented. Each physiographic area supports a different vegetation community, also separated by sharp boundaries. The present structure of two communities, Melaleuca howeana scrub and Howea forsterana forest, is a consequence of damage by feral animals. Melaleuca scrub has replaced Cyperus lucidus sedgeland destroyed by goats (Capra hircus) browsing from 1914 until their extermination in 1955. Howea forest has a markedly unimodal age distribution with very few small individuals of the dominant palms. This is a result of the combined effects of browsing by goats on small palms, and seed predation by black rats (Rattus rattus) from the 1920s, preventing regeneration. Unless rat numbers are periodically reduced to reduce seed predation, regeneration may be insufficient to guarantee long‐term survival of the forest.


title: Suburban development and change in vegetation nutritional status

text: In a study of species presence/absence and soil properties in bushland around northern Sydney, Clements (1983) found that species groupings were related to total soil phosphorus. This report presents analysis of foliage nutrient concentrations in species within these groupings. The highest concentrations of phosphorus, calcium, magnesium and potassium occurred in the suburban/disturbed group. The lowest overall concentrations were found in foliage from species in the dry sclerophyll communities. Mean foliage phosphorus was 0.099%, 0.125% and 0.042% for wet sclerophyll, disturbed and dry sclerophyll groups, respectively. Exotic species, particularly in disturbed environments, had the highest foliage nutrient concentrations. Results presented here showed that foliage nutrient concentrations are consistent with definitions of these groups on the basis of total soil phosphorus. These changes are considered to be important for management and conservation of bushland areas around Sydney.


Gammacoronavirus(‡): Coronaviridae


title: Inotropic Support in the Treatment of Septic Myocardial Dysfunction: Pathophysiological Implications Supporting the Use of Levosimendan

text: Myocardial dysfunction is a frequent organ manifestation during septic shock and the subsequent impairment in cardiac output may result in organ hypoperfusion, requiring prompt and adequate treatment to restore cardiovascular function and reverse shock [1]. Current sepsis guidelines recommend resuscitation with intravascular fluid administration in association with inotropes and vasopressors to maintain organ perfusion [2]. Dobutamine is recommended as first-line inotropic agent and should be administered when low cardiac output or signs of hypoperfusion persist after adequate fluid resuscitation and perfusion pressure have been achieved [2]. However, the efficacy of dobutamine in patients with heart failure has not been fully demonstrated and concerns on its use are still present [3]. Although dobutamine improves perfusion and increases oxygen delivery (DO(2)), its impact on survival in septic shock patients is limited, with guideline recommendations based mainly on the landmark study by Rivers et al. [4]. Recently, Wilkman et al. [5] reported that the use of inotropes, particularly dobutamine, in septic shock was associated with increased 90-day mortality. In explaining the lack of outcome benefit [3, 5], several aspects need to be taken into account. First, the need of inotropic support may simply represent an expression of disease severity rather than the cause of a poor outcome. Second, whereas the treatment of impaired cardiac output should be tailored based on the etiological mechanism of the cardiovascular dysfunction, the current guidelines recommend the use of inotropes without differentiating the underlying causes of impaired left ventricular (LV) stroke volume [2, 6]. In addition, the majority of cardiovascular monitoring instruments provide data almost exclusively on cardiac output and pressures. This approach may potentially increase the number of patients who may be harmed by inotrope administration (Fig. 1). Finally, the beneficial short-term effect of enhanced contractility by cAMP-increasing drugs (e. g., dobutamine, milrinone) is, at least partly, abolished by the increased energy consumption, the worsening of ventricular relaxation and the direct cardiomyocyte toxicity [1, 7–10].


title: Dynamics of Regional Lung Inflammation: New Questions and Answers Using PET

text: The meaning of the term ‘inflammation’ has undergone considerable evolution. It was originally defined around the year 25 A.D. by Aulus Cornelius Celsus [1] and described the body’s acute reaction following a traumatic event, such as a microscopic tear of a ligament or muscle. His original wording: “Notae vero inflammationis sunt quatour: rubor et tumor cum calore et dolore” (true signs of inflammation are four: redness and swelling with heat and pain) still holds. Disturbance of function (functio laesa) is the legendary fifth cardinal sign of inflammation and was added by Galen in the second century A.D. [2]. Recent articles [3] highlight the complicated role that inflammation plays in chronic illnesses, including metabolic, cardiovascular and neurodegenerative diseases. In addition to these difficult-to-treat diseases, more research and research tools are needed to illuminate therapeutic strategies in another difficulty-to-treat inflammatory malady, the acute respiratory distress syndrome (ARDS).


title: RNA Higher-Order Structures Within the Coronavirus 5′ and 3′ Untranslated Regions and Their Roles in Viral Replication

text: The 5′ and 3′ untranslated regions (UTRs) of all coronaviruses contain RNA higher-order structures which play essential roles in viral transcription and replication. In this chapter we present our current knowledge of how those cis-acting elements were defined and their functional roles in viral transcription and replication. Cellular proteins which have been shown binding to those cis-acting elements and potentially support the RNA discontinuous synthesis model are also discussed. A conserved RNA structure model for the 5′ and 3′ UTRs of group 2 coronaviruses is presented with the known cellular protein binding sites.


title: Molecular biological tests

text: Molecular biological testing has become a mainstay in the repertoire of infectious disease diagnostics like in no other field of medicine. Direct pathogen detection primarily relies upon two main methods: the polymerase chain reaction (PCR) and immunochromatography – often supplied as test strips or test cards. Alongside pathogen detection, the PCR method has the advantage that it can simultaneously analyze resistance determinants and/or virulence factors. In the age of multidrug-resistant (nosocomial) pathogens, rapid and reliable molecular biological differentiation is becoming increasingly important given the urgency indicated to effectively isolate affected patients at the earliest possible chance.


title: Laboratory Safety and Biohazards

text: All laboratories have potential hazards, and the importance of understanding lab safety cannot be emphasized strongly enough. Scientists are expected to understand and be aware of the health and safety issues associated with their profession. Regardless of the standards for laboratory safety in their country of origin and regardless of their position, all researchers require a good understanding of safety features in English before they can begin working in an English-speaking laboratory. All research institutions in English-speaking countries require all new staff to go through a safety orientation or training course before they can begin work. Your employer or institution has a legal requirement to provide you with safety training before you begin work. Generally, a safety officer, a person who acts as the institutional or departmental administrator for safety-related matters, gives the course, and a written safety test must be completed by all new employees following training before work can commence in the laboratory. It is your legal duty to cooperate with your employer or institution’s efforts to improve safety in the workplace. Not respecting safety regulations and procedures while working in a laboratory does not only put your own health and others’ at risk, but it may also have an impact on the lab’s license and may lead to disciplinary action against you. Everyone must be aware and responsible so we can all enjoy our research while staying safe!


Rotavirus and Noro- and Caliciviruses


title: The Cell Biology of the SARS Coronavirus Receptor, Angiotensin-Converting Enzyme 2

text: The identification of angiotensin-converting enzyme 2 (ACE2) as a cellular receptor for the SARS coronavirus (SARS-CoV) rejuvenated research into what was regarded by some as a minor player in the renin–angiotensin system. The discovery of its double life led to breathtaking advances in the understanding of virtually all aspects of its biology, including its structure, physiological and pathophysiological roles and cell biology. ACE2, like its well-known homologue, ACE, is a metallopeptidase which resides on the cell surface of the epithelial, and sometimes endothelial, cells of the heart, kidney, testes, lung and gastrointestinal tract. It is a type I transmembrane protein with a large catalytic extracellular domain which acts as both a peptidase and a viral receptor. This extracellular domain can be cleaved from the cell surface by other peptidases, modulating its activity. The levels of the enzyme on the cell surface are also thought to be regulated by internalisation on S-protein binding and by clustering in membrane microdomains known as lipid rafts. This chapter summarises the current understanding of how the cell biology of ACE2 is regulated and may influence and determine its function, and concludes by discussing the future challenges and opportunities for studies of this increasingly important enzyme.


docid: welsrjao

title: Corticosteroids as Adjunctive Therapy in Severe Community-Acquired Pneumonia

text: Mortality in community acquired pneumonia (CAP) has not decreased in the intensive care unit (ICU), despite progress in antimicrobial therapy [1, 2]. Approximately 10% of patients hospitalized with CAP are admitted to the ICU [3]. In a multicenter study by Mongardon et al. in patients with severe pneumococcal CAP admitted to the ICU, the mortality rate was 29%, with high proportions of patients in septic shock and needing mechanical ventilation [4]. Severe CAP is a progressive disease and patients may die despite early and adequate antibiotic treatment. The host local and systemic inflammatory immune response in patients with severe CAP is exacerbated and disproportionate and this is probably the main cause for the high mortality in this specific population, as it contributes to impaired alveolar gas exchange, sepsis and end-organ dysfunction [5]. In this specific population of patients with severe CAP, adjuvant treatments, such as corticosteroids, may be beneficial.


title: Management of Malignant Pleural Effusions

text: The development of pleural effusions is a common occurrence in patients with neoplastic disease. In one postmortem study, 15 % of patients who died with malignancies were found to have malignant pleural effusions, and the annual incidence of malignant pleural effusions (MPE) in the United States is estimated to be >150,000 cases. The presence of a MPE often portends a poor prognosis; the mean survival after the diagnosis of a MPE ranges from 3 to 12 months, depending on the underlying tumor (lung cancer is generally associated with the shortest average survival time). Patients with MPE often have symptoms that impair their quality of life, such as dyspnea, orthopnea, cough, and chest discomfort, some or all of which can be improved with palliative therapeutic measures.


title: Virale Gastroenteritiserreger

text: Gastroenteritiden gehören zu den häufigsten Erkrankungen des Menschen und sind mit einer hohen Krankheitslast und Mortalität verbunden. Besonders betroffen sind Säuglinge und Kleinkinder in den Tropen, wo jährlich schätzungsweise 1–2 Mio. Kinder an einer Gastroenteritis versterben. Viren gehören zu den häufigsten Auslösern dieser Erkrankungen. Seit der elektronenmikroskopischen Entdeckung des Norwalkvirus 1972 wächst die Zahl der bekannten Erreger.


title: Verloskunde

text: In dit hoofdstuk worden door een gynaecoloog en verloskundige de fysiologie en pathologie van de verloskunde per tijdperk op een beknopte, heldere wijze behandeld. Dat zijn achtereenvolgens de zwangerschap, het ontsluitingstijdperk, het uitdrijvingstijdperk, het nageboortetijdperk en het kraambed. Elk onderdeel sluit af met een bespreking van de belangrijkste therapeutische interventies.


title: SARS Coronavirus Spike Protein Expression in HL-CZ Human Promonocytic Cells: Monoclonal Antibody and Cellular Transcriptomic Analyses

text: The SARS coronavirus (CoV) spike protein is a target of intensive research, as it is a major virulence factor. Transfection of SARS-CoV spike into Vero E6, HEK293T and HL-CZ cells leads to strong expression of the glycosylated spike protein, as shown by Western blot analyses and immunofluorescent imaging using spike-specific human monoclonal antibodies, indicating the potential utility of these antigens and antibodies as diagnostic reagents. Furthermore, we employed cDNA microarray analysis to probe the changes in host gene transcription attributed to transfection of a codon-optimized spike construct into the HL-CZ cell line of monocyte lineage that is linked to immunological responses. A diverse representation of 100 genes displayed altered transcriptional patterns in response to SARS-CoV spike expression, with 61 upregulated and 39 downregulated genes. Genes involved in intracellular trafficking, signaling, modulation or transcription were generally upregulated. In contrast, genes involved in cell metabolism and cytoskeleton formation were notably downregulated. The transcripts of other functional categories exhibited varied responses to SARS-CoV spike transfection. Collectively, our analyses elucidate numerous and complex transcriptomic events that occur in response to spike protein expression and that contribute towards SARS-CoV pathogenesis.


title: Amino Acid Transport by Epithelial Membranes

text: This review summarizes the current view of amino acid transport by epithelial cells of vertebrates. A wide variety of transporter proteins are expressed in apical and basolateral membranes and collectively play complex interactive roles in controlling the entire organism’s overall metabolism of amino acids. Regulation of the transport systems can be manifested at many levels, including gene splicing and promoter regulation, interactions between requisite subunits of oligomers, thermodynamic electrochemical gradients contributed by ion exchangers, overlap of substrate specificity, selective tissue distribution, and specific spatial distribution of transporters leading to net vectorial flow of the amino acids. The next frontier for workers in this field is to uncover a comprehensive molecular understanding of the manner by which epithelial cells signal gene expression of transporters as triggered by substrates, hormones or other triggers, in order to further understand the trafficking and interactions among multimeric transport system proteins, to extend discoveries of novel small drug substrates for oral and ocular delivery, and to examine gene therapy or nanotherapy of diseases using small molecules delivered via amino acid transporters.


2009-H1N1


title: Infektiologie

text: Nachdem in den letzten Jahren v. a. klinisch-chemische Parameter (z. B. Blutglukose, Blutgase, Elektrolyte, kardiale Marker) von den Erweiterungen im POCT-Bereich profitiert haben, hält diese Form der Analytik mehr und mehr auch im Bereich der Infektiologie Einzug. In aller Regel sind mikrobiologische Tests im POCT-Format als sog. Schnelltests konzipiert. Ein solcher Test kann i. Allg. mit wenigen einfachen Arbeitsschritten von medizinischem Assistenzpersonal oder von Ärzten ohne Laborgeräte oder Laborerfahrung durchgeführt werden, gelegentlich ist sogar eine Anwendung durch den Patienten selbst möglich.


title: SARS Coronavirus Replicative Enzymes: Structures and Mechanisms

text: The SARS coronavirus (SARS-CoV) replicase gene encodes 16 nonstructural proteins (nsps) with multiple enzymatic activities. Several of these enzymes are common components of replication complexes of other plus-strand RNA viruses, such as picornavirus 3C-like protease, papain-like protease, RNA-dependent RNA polymerase, RNA helicase, and ribose 2′-O-methyltransferase activities, while others such as exoribonuclease, endoribonuclease, and adenosine diphosphate-ribose 1″-phosphatase activities, are rarely or not conserved in viruses outside the order Nidovirales. The latter enzymes are believed to be involved in unique metabolic pathways used by coronaviruses to (1) replicate and transcribe their extremely large RNA genomes, and (2) interfere with cellular functions and antiviral host responses. Since the global outbreak of SARS in 2003, major efforts have been made to elucidate the structures of the protein components of the SARS-CoV replication/transcription complex. Thus, in less than 5 years, the structures of as many as 16 SARS-CoV proteins or functional domains have been determined. Remarkably, eight of these 16 structures had novel folds, illustrating the uniqueness of the coronavirus replicative machinery. Furthermore, several new protein functions and potential drug targets have been identified in these studies. Current structural studies mainly focus on the few remaining proteins for which no structural information is available and larger protein complexes comprised of different nsps. The studies aim at obtaining detailed information on the functions and macromolecular assembly of the coronavirus replication/transcription machinery which, over a long period of time, may be used to develop selective antiviral drugs. This chapter reviews structural information on the SARS-CoV macro domain (ADRP) as well as nsps 7, 8, 9, and 15 and summarizes our current knowledge of active-site residues and intermolecular interactions of these proteins.


title: Coronaviren

text: Man unterscheidet 6 humanpathogene Coronaviren, die entweder zum Genus Alpha-Coronavirus oder zum Genus Beta-Coronavirus gehören (Subfamilie Coronavirinae, Familie Coronaviridae). Humane Coronaviren verursachen akute respiratorische Erkrankungen, die meist problemlos verlaufen, gelegentlich jedoch zu schweren Pneumonien führen, insbesondere bei bestehender Komorbidität oder bei Infektionen mit spezifischen humanen Beta-Coronaviren. Eine ursächliche Beteiligung an Gastroenteritiden ist möglich, spielt jedoch klinisch und zahlenmäßig keine große Rolle. Die zahlreichen bekannten animalen Coronaviren verursachen in der Regel respiratorische und gastrointestinale Erkrankungen, insbesondere bei Säugetieren und Vögeln. Der Name der Viren leitet sich vom typischen elektronenmikroskopischen Erscheinungsbild der Virusoberfläche ab, die an eine Krone (lat. »corona«) erinnert. Die Fortsätze dieser Krone werden von den viralen Glykoproteinen, sog. Spikes, gebildet, die in die Virushülle eingelagert sind. Coronaviren sind Plusstrang-RNA-Viren mit den größten Genomen (30 kb) unter allen bekannten RNA-Viren. Sie haben einen Durchmesser von etwa 120 nm. Das helikale Kapsid wird von einer Lipidhülle umgeben, in die mindestens 3 Strukturproteine (Spike-Glykoprotein S, Hüllprotein E, Membranprotein M) eingelagert sind.


Rapid Detection of Bioterrorism Pathogens


title: Pneumonia Virus of Mice (PVM): Exploring Novel Therapeutic Options In a Severe Respiratory Disease Model

text: Respiratory syncytial virus (RSV) is the most important respiratory pathogen among infants and toddlers, with infections prevalent and nearly universal in this age group. Severe infections are more common among premature infants, those with cardiac and pulmonary anomalies, and the immunosupressed. Effective prophylactic monoclonal antibody treatment is available for high-risk infants, but there is no effective vaccine. Mouse challenge models have been used for the study of the human RSV pathogen, but the most severe forms of RSV disease are not replicated by this approach. Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a mouse pathogen of the same family as human respiratory syncytial virus. PVM replicates efficiently in mouse-lung epithelial cells in vivo in response to a minimal virus inoculum, and replication is accompanied by local production of proinflammatory cytokines (MIP-1α, MIP-2, MCP-1, and IFN-γ) and granulocyte recruitment to the lung. PVM infection and the ensuing inflammatory response can lead to pulmonary edema and respiratory compromise. Our laboratories have pioneered the use of the PVM model for the study of human clinical disease, which has provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. As part of this work, we have presented several immunomodulatory strategies that clearly reduce morbidity and mortality when administered to PVM infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe RSV infection in human subjects.


title: A Brief History of Microbiology and Immunology

text: Vaccine history is inextricably linked with the histories of microbiology and immunology; evolution of the latter disciplines parallels the ongoing quest of humankind to understand the fundamental basis of life. How our species survives in the hostile world that surrounds us has been a source of fascination since the beginning of recorded time. Injury and infection likely exacted a heavy toll as our early hominid ancestors descended from the trees and adapted a predatory life style on the African plains; death from bleeding and wound infections undoubtedly plagued early humans (Opal 2003). Epidemic disease, however, probably played a minor role in shaping the primitive human immune system. Instead, the primary determinants of lethality for small, scattered bands of hunter-gatherer populations of Homo sapiens were starvation, predation, and hypothermia.


title: Structured Approach to Early Recognition and Treatment of Acute Critical Illness

text: Well-known global health priorities (malaria, pneumonia, sepsis, diarrhea, human immunodeficiency virus [HIV], tuberculosis, trauma), although very different threats to an individual’s health, share a common consequence: Development of acute, life-threatening illness. In the developed world, such illness is routinely treated in an intensive care unit (ICU) by highly specialized physicians, nurses and support staff. This model of intensive care is spreading rapidly to low and middle income countries and as it spreads, challenges and limitations to this model arise [1].


title: SARS Coronavirus Accessory Gene Expression and Function

text: Coronavirus genomes are single-stranded positive-sense RNA that are transcribed into a nested set of 3′ coterminal subgenomic RNAs for gene expression. Members of the Coronaviridae express canonical polymerase genes, as well as structural genes, including S, E, M, and N, but also express a highly divergent set of accessory genes whose open reading frames are interspersed among the structural genes within the 3′ one-third of the viral genome. The accessory genes are thought to contain “luxury” functions that are often not required for in-vitro virus replication. The severe acute respiratory syndrome coronavirus (SARS-CoV) expresses eight such accessory genes (ORF3a, -3b, -6, -7a, -7b, -8a, -8b, and -9b), the most of any known coronavirus. This chapter will review our current knowledge of expression, structure, and function of each of the SARS-CoV accessory genes.


Torovirus(‡): Coronaviridae


title: Electrolytes, Fluids, Acid-Base Analysis, and Transfusion Therapy

text: Understand the risks and benefits of fluid replacement therapy options. Know how to calculate a patient’s fluid requirements and allowable blood loss. Learn the types of blood transfusion therapy available and their indications


Betacoronavirus(‡): Coronaviridae


title: Pneumonien

text: Pneumonien im Kindesalter sind häufig; je nach geographischer Region kann die Sterblichkeit an Pneumonien bis 2 Millionen pro Jahr betragen, das sind weltweit rund 30% aller Sterbefälle bei Kindern bis zum 5. Lebensjahr. In Mitteleuropa und den USA erkranken ca. 30/10.000 Kinder unter 5 Jahren jährlich an einer Pneumonie, für die Altersgruppe 0–16 jährig beträgt die Inzidenz etwa 15/10.000 Kinder.


title: Critically Ill Patients with Middle East Respiratory Syndrome Coronavirus Infection

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that may lead to severe acute respiratory illness frequently associated with multiorgan failure and death. The objective of this chapter is to summarize the current state of knowledge regarding the pathogenesis, clinical manifestations, diagnosis, management and outcomes of MERS-CoV infection focusing on the critically ill.


title: Bewegung und Erkrankungen des Immunsystems

text: Die Effektivität von körperlicher Aktivität in der Primär- als auch Sekundär- und Tertiärprävention ist hinlänglich bekannt. Das Immunsystem spielt eine entscheidende Rolle bei einer Vielzahl von Erkrankungen, da es durch seine Botenfunktion (z. B. durch Zytokine) in einer Vielzahl der Regulationsprozesse mit involviert ist. So kommt es durch moderat-intensive körperliche Aktivität zu einer Stärkung des Immunsystems mit konsekutiv verminderter Infektanfälligkeit sowie eher anti-inflammatorischen Effekten, wohingegen langandauernde und höher intensive Belastungen zu einer Schwächung der Abwehrfunktion sowie einem pro-inflammatorischen Effekt führen. Somit stellt eine adäquat dosierte körperliche Aktivität eine erfolgversprechende Therapieoption bei Erkrankungen des infektiologischen Formenkreises sowie des Immunsystems dar.


title: Imaging of Chest Infections in Children

text: ■ Imaging studies have limited value in the differentiation between viral and bacterial lower respiratory tract infections (moderate evidence). ■ CT provides more information than plain radiographs for complicated pulmonary infections with empyema, pleural effusion, or bronchopleural fistula (moderate evidence). ■ In immunocompromised patients, CT has been shown to characterize the type of infection better than plain radiographs (moderate evidence). ■ Ultrasound has an advantage over CT in the identification and characterization of complicated effusions (moderate evidence). ■ Early detection and therefore intervention for pleural complications of pneumonia are critical and can result in better outcomes (moderate evidence). ■ Early surgery (VATS) is more cost-effective than thoracotomy (without or with image guidance) in the treatment of empyemas in children (strong evidence).


docid: obvhejkq

title: Modulation of Host Cell Death by SARS Coronavirus Proteins

text: Both types of cell death, namely necrosis and apoptosis, are found in organs of SARS coronavirus (CoV) infected patients. The gastrointestinal tract, however, although also a target for SARS-CoV replication, is obviously not affected by cell death mechanisms. Such differences in cell death induction are paralleled by in-vitro studies. In a colon-derived cell line (Caco-2), proapoptotic proteins were down- and antiapoptotic proteins were upregulated during SARS-CoV infection. By contrast, in SARS-CoV infected Vero E6 cells, apoptosis was induced via the p38 MAPK and caspase dependent pathways. Both apoptotic pathways, although mostly the intrinsic signal transduction, can be targeted by structural as well as accessory proteins of SARS-CoV. The fact that all structural and most of the accessory proteins of SARS-CoV are implicated in apoptotic scenarios indicates the fundamental role of apoptosis in the SARS-CoV life cycle. Interestingly, at least for the nucleocapsid protein of SARS-CoV, a cell-type specific manipulation of apoptosis was confirmed.


title: Was bitte ist denn »Molekularbiologie«?

text: In diesen Zeiten Molekularbiologie zu betreiben ist aufregend. Es bedeutet »Gentechnik« und »Klonieren« und hat etwas Göttliches. Beim einen Teil der Bevölkerung wird man, wenn man verrät, womit man seinen lieben langen Arbeitstag verbringt, grenzenlose Bewunderung hervorrufen, beim anderen grenzenlose Ablehnung – man sollte sich daher genauestens überlegen, mit wem man es gerade zu tun hat, bevor man den Mund aufmacht. Am besten, man erwähnt keiner der Gruppen gegenüber, mit wieviel Problemen und Frust man in Wahrheit täglich kämpft, weil der erste Teil dann desillusioniert wäre und der zweite, vielleicht zurecht, unweigerlich die Frage stellen würde: »Wozu machst du das dann überhaupt?«


Public Health Surveillance for Bioterrorism


title: Infectieziekten

text: In dit hoofdstuk worden de ziektebeelden op het gebied van de infectieziekten op een beknopte, heldere wijze behandeld door een aantal vakexperts en een huisarts, de beste combinatie om de klinische relevantie voor de huisartsenpraktijk te waarborgen. De volgorde van de paragrafen is alfabetisch. Aan het eind van het hoofdstuk worden de belangrijkste infecties met multiresistente bacteriën (MRSA, VRE, e.d.) genoemd. Voor specifieke therapie wordt verwezen naar ▶ H. 10.1007/978-90-368-0610-7_25 Antimicrobiële therapie.


title: Bronchoalveolar Lavage

text: Bronchoalveolar lavage (BAL) is a minimally invasive procedure and plays an important role in the diagnostic evaluation of interstitial lung disease, pulmonary infiltrates, and some infectious diseases. The decision to perform bronchoscopy and BAL should be guided by clinical presentation and the patient’s status as well as local technical expertise, both in performing the procedure and in interpreting the results. An important problem with interpreting BAL results is the variability between centers, which highlights the importance of following standard protocols. There is a need for a consensus statement among experts to provide guidelines for the utility of BAL cellular analyses in clinical practice. A number of specific conditions, such as some rare diseases, malignancy, and infections, can be diagnosed by BAL analyses. In such cases, more invasive procedures can be avoided. Even when nondiagnostic, BAL cellular analysis usually adds valuable information to the clinical and radiological data and helps to narrow the differential diagnosis. On the other hand, the diagnostic usefulness of BAL in interstitial lung disease, especially idiopathic pulmonary fibrosis (IPF), is limited. An important issue of BAL in this setting is exclusion of other diseases as sarcoidosis or hypersensitivity pneumonitis. BAL is an invaluable research tool for ILD, providing information regarding immune effector cells that accumulate in the alveoli and their noncellular products. With the increasing availability of proteomics, the importance of biomarkers of ILD will hopefully become clear in the near future. It is essential that BAL findings be interpreted by experts in the context of clinical and radiological data.


title: Infectious diseases

text: The measurement of biochemical parameters such as blood glucose, blood gases, electrolytes and cardiac markers have particularly benefited from recent advances in POCT. More and more, this form of analysis is now positively impacting the field of infectious diseases. Many microbiological POCT systems tend to be designed as rapid tests. In general, such tests can be carried out in a few simple steps by medical assistants or physicians without laboratory equipment or laboratory experience. It is even possible for the patients themselves to perform a series of such tests.


title: International Distribution

text: When business historians look back at the period of the last 10 years of the twentieth century and the first decades of the new millennium, one of the most salient developments will be the emergence of the global economy. For several decades after the Second World War, companies rarely ventured outside their own national boundaries. While some of the world’s largest corporations, such as Coca-Cola, Ford Motor Company, and Procter & Gamble, had historically engaged in a significant international trade, governments were fearful of exporting technologies, core skills, product, and wealth that might drain national resources in the face of the Cold War. In many cases, enormous markets, such as Eastern Europe, Russia, and China, were closed behind a seemingly impenetrable “iron curtain.” Today, the Cold War has long been part of history. Some of the world’s most vibrant economies, such as China, Brazil, and India, have emerged from behind once closed societies to engage billions of people in global commerce in the search for individual as well as national growth and well-being. The advent of connective technologies have enabled companies at the furthest ends of the earth to network their ideas and their businesses in real-time, accelerate the growth of the international marketplace, and integrate the world’s economic activities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this chapter (doi:10.1007/978-1-4899-7578-2_14) contains supplementary material, which is available to authorized users.


title: Molecular Epidemiology

text: Molecular epidemiology is now an established discipline in epidemiology.(1) It is the contemporary stage in the evolution of laboratory-based epidemiology that may have begun with the discovery in the late 1800s of ways to differentiate bacterial organisms by pure culture in artificial media.(2) Molecular epidemiology uses new molecular biology tools to address questions difficult or not possible to address by old laboratory tools. Just as statistical tools have become indispensable in epidemiological investigations and interpretations of epidemiologic data, molecular biology tools today have come to elucidate epidemiologic features of diseases that cannot be easily characterized by conventional techniques. Applied to infectious diseases, molecular biology methods have also come to challenge our traditional notions about the epidemiology of these diseases and have engendered novel opportunities for their prevention and control. This chapter will (1) review definitions commonly used in molecular epidemiology, (2) present an overview of molecular biology methods used to study infectious disease epidemiology, and (3) describe examples of the types of epidemiologic problems that can be addressed by molecular biology techniques, highlighting new concepts that emerged in the process of applying this approach to study bacterial infectious diseases.


title: Global Immunization Challenge: Progress and Opportunities

text: After reading this chapter and answering the discussion questions that follow, you should be able to: Outline important milestones in the emergence of vaccines as a means of disease control and prevention. Discuss factors that underpin the disparity in access to vaccines between rich and poor countries. Identify and appraise innovative options for financing vaccine development, and for ensuring wider access to new and underused vaccines in developing countries. Evaluate strategies for ensuring sustainability in vaccine development, management, and access. Outline priorities for future research, policy, and practice with regard to vaccine development, procurement, and access.


title: Virusinfektionen

text: Dieses Kapitel behandelt Klinik, Komplikationen, Diagnostik, Prophylaxe und Therapie der wesentlichen Virusinfektionen im Kindes- und Jugendlichenalter, u. a. Virusinfektionen der Herpes-Gruppe (HSV1 und 2 [u. a. schwere neonatale Infektionen, Herpesenzephalitis]), VZV [u. a. neonatale VZV-Infektionen, Herpes-Zoster], EBV, CMV, HHV6–7 [Dreitagefieber], HHV8 [Kaposi-Sarkom]. Unter den Virushepatititiden spielen bei Kindern die Hepatitis A, B (chronische Hepatitis B) sowie C (chronische Hepatitis B) die größte Rolle. Weitere bedeutsame Viren sind Parvovirus-B19 (Ursache der Ringelröteln, einer aplastischen Krise oder eines Hydrops fetalis), humane Papillomaviren (bedeutsam v. a. Genitalwarzen, Larynxpapillome und Karzinome), Rotaviren (bedeutsame Gastroenteritiserreger), FSME, HIV sowie die „typischen Kinderkrankheiten“ Masern, Mumps und Röteln. Häufige Erreger des oberen und unteren Respirationstrakts sind Rhinoviren, das RS-Virus, das humane Metapneumovirus (hMPV), das humane Bocavirus (hBoV), das humane Coronavirus (HCoV) sowie Influenza- und Parainfluenzaviren.


Alphacoronavirus(‡): Coronaviridae


title: Molecular Microbiological Testing

text: The application of molecular testing methods in the clinical laboratory has dramatically improved our ability to diagnose infectious diseases. Nucleic acid techniques, such as plasmid profiling, various methods for generating restriction fragment length polymorphisms and the polymerase chain reaction (PCR) are making increasing inroads into clinical laboratories. However, the clinical usefulness of molecular testing will only be maximized to its fullest benefit by appropriate and careful studies correlating clinical findings with assay results.


title: Leber

text: Leberabszesse stellen immer noch eine sehr ernsthafte Erkrankung dar, auch wenn die Mortalität durch Fortschritte in Diagnostik und Therapie deutlich gesenkt werden konnte. Bei der Diagnosestellung spielen Ultraschall und CT die Hauptrolle, bei Bedarf ergänzt durch ERCP/MRCP. Die Diagnostik von Grund- und Begleiterkrankungen ist für Prognose und kuratives Vorgehen oft entscheidend. Antibiotische Therapie und perkutane Drainage bilden die Hauptsäulen der Behandlung, ein chirurgisches Vorgehen ist besonders im Rahmen der Sanierung von Grunderkrankungen und bei therapierefraktären Fällen notwendig. Die Leberblutung ist eine klassische Komplikation des Leberzelladenoms, tritt aber auch bei anderen Lebertumoren (z. B. hepatozelluläres oder cholangiozelluläres Karzinom) auf. Oft wird die Diagnose bei einer Ultraschalluntersuchung im Schockraum gestellt; wenn genügend Zeit vorhanden ist, kommt eine CT zur weiteren Diagnostik infrage. Die rasche operative Versorgung ist für den positiven Ausgang entscheidend.


title: Airline Culture: International Flight Attendant Service Design

text: The author is Japanese. She became interested in service development for airlines while employed as a member of the cabin crew by an airline (here called H), which while based in Europe flies to Japan. Based on that experience combined with subsequent fieldwork, the research reported here explores changes in the culture of cabin service, paying particular attention to the personal agency exercised by a subset of cabin crew members who are Regional Flight Attendants responsible for providing local language and culturally sensitive service to passengers from their homelands, as they have responded to a changing airline industry environment. Today’s airlines are deeply embedded in the global circulation of people, goods, and capital. They have also been primary actors in promoting changes in their own global culture. As the process of creating a global “airline civilization” has unfolded, they have been forced repeatedly to restructure their organizations in response to changes in their business environment. These changes have strongly influenced both the nature of cabin service and the working conditions of cabin crew members. On the one hand, their jobs have become more demanding. On the other, they have, through service design, maintained a certain distance from their work and continue to enjoy the freedom it offers. They face increasingly stiff demands but remain grateful to the airline for providing the opportunities they enjoy.


title: Influenza A (H1N1)

text: In the summer of 2009 a 12-year-old boy with a history of multiply relapsed acute lymphoblastic leukemia now in his fourth remission on an individualized chemotherapy protocol, presented to his local hospital’s emergency room with a two day history of fever to 102.5°C (39.2°C) and upper respiratory symptoms including cough, sore throat, and runny nose. His mother developed similar symptoms approximately one week ago. In addition, he complained of abdominal pain with persistent diarrhea and one episode of emesis. The patient had a history of obstructive lung disease of uncertain etiology for which he used an albuterol inhaler on an “as needed” basis. Since the onset of this acute illness he had been using his inhaler every four hours.


title: Adenoviren

text: Alle Adenoviren sind unbehüllte DNA-Viren mit ca. 35 kb großem Genom. Die über 70 Typen unterscheiden sich genetisch stark und verursachen je nach Typ akute Erkältungskrankheiten, Pharyngitis, Konjunktivitis, Keratokonjunktivitis, Gastroenteritis, hämorrhagische Zystitis, Pneumonien, selten auch Meningitis und Enzephalitis. Adenoviren interferieren mit dem Angriff des Immunsystems auf infizierte Zellen und persistieren mehrere Jahre asymptomatisch in den Tonsillen (»Adenoiden«). Bei Immunsuppression können sie reaktiviert werden und dann lebensbedrohlich disseminieren.


title: Viral Sepsis

text: Viruses are the smallest infective agents currently known to affect humans and animals. The virus has a centrally situated nucleic acid, which is encased within a capsid consisting of a protein core. Viruses are obligatory intracellular microorganisms that live inside cells, using components of the nucleic acid and protein generating system of the host to replicate and trigger cell destruction leading to diseases. Alternatively, the host’s defense mechanisms lead to cell destruction in an attempt to clear cells infected by the viruses. The nucleic acid is RNA or DNA, which may be single-stranded or double-stranded [1]. The pathophysiology of viral infections may be attributed to the degeneration and cellular necrosis of the infected cells, leading to local and systemic inflammatory responses. The body’s defense mechanisms include phagocytosis, humoral and cell-mediated responses and the production of interferons [2]. Interferons prevent the local spread of viruses, whereas antibodies prevent viremia, ensure long-term immunity and sensitize infected cells to be destroyed by T-cells and macrophages [3, 4]. Cell-mediated immunity leads to an increase in cytotoxic cells that then release lymphokines, including interferon.


docid: fakapdcc

title: Programmed –1 Ribosomal Frameshifting in SARS Coronavirus

text: In coronaviruses such as the SARS coronavirus (SARS-CoV), programmed −1 ribosomal frameshifting (−1 PRF) is used to direct the synthesis of immediate early proteins, e.g., RNA-dependent RNA polymerase (RDRP) and proteases, that are thought to prepare the infected cell for takeover by the virus. Unlike other RNA viruses which make their structural proteins first, this class of proteins is synthesized after −1 PRF, from subgenomic mRNAs produced subsequent to production of RDRP. Also unique among the coronaviruses is the inclusion of mRNA structural elements that do not appear to be essential for frameshifting. Understanding the differences between –1 PRF signals from coronaviruses and other viruses will enhance our understanding of –1 PRF in general, and will be instructive in designing new classes of antiviral therapeutics. In this chapter we summarize current knowledge and add additional insight to the function of the programmed –1 ribosomal frameshift signal present in the SARS-associated coronavirus.


title: Novel Pharmacologic Approaches for the Treatment of ARDS

text: Acute respiratory distress syndrome (ARDS) is a heterogeneous disease, which is defined by the acute onset of hypoxemic respiratory failure with bilateral infiltrates on chest radiography due primarily to non-cardiogenic pulmonary edema [1]. Only two supportive strategies have shown to improve survival in patients with acute lung injury (ALI)/ARDS, namely lung protective ventilation that reduces the stretch of the lungs and a conservative fluid strategy [2, 3]. The mortality of ARDS, however, remains high and no pharmacological therapies have effectively improved the outcome of these patients so far. Studies of the pharmacologic management of ARDS, such as trials of anti-inflammatory agents, anticoagulants, surfactant, vasodilators, and β(2) agonists, have shown conflicting results [4]. Potential reasons for such conflicting results may be: In the last decade, there has been extensive research into potential therapeutic targets and methods of drug administration that could help in the development of specific pharmacological drugs to prevent or mitigate the development of ARDS.


title: The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential

text: As in other coronaviruses, the nucleocapsid protein is one of the core components of the SARS coronavirus (CoV). It oligomerizes to form a closed capsule, inside which the genomic RNA is securely stored thus providing the SARS-CoV genome with its first line of defense from the harsh conditions of the host environment and aiding in replication and propagation of the virus. In addition to this function, several reports have suggested that the SARS-CoV nucleocapsid protein modulates various host cellular processes, so as to make the internal milieu of the host more conducive for survival of the virus. This article will analyze and discuss the available literature regarding these different properties of the nucleocapsid protein. Towards the end of the article, we will also discuss some recent reports regarding the possible clinically relevant use of the nucleocapsid protein, as a candidate diagnostic tool and vaccine against SARS-CoV infection.


title: Plotselinge uitbraken

text: Er is sprake van een plotselinge uitbraak als het aantal nieuwe ziektegevallen in een bepaald geografisch gebied in een relatief korte tijd sterk toeneemt. Epidemiologisch onderzoek naar uitbraken kent ook zijn eigen onderzoeksdesigns en analysemethoden. Een belangrijke toepassing is de infectieziekte-epidemiologie die bovendien een eigen terminologie hanteert zoals: incubatie, latentie, ‘attack-rate’, transmissie en het basaal reproductiegetal. Het hoofdstuk beschrijft verschillende surveillancesystemen om tijdig alarm te kunnen slaan bij een plotselinge uitbraak, zowel in Nederland als in de wereld. Het geeft bovendien een overzicht van de verschillende ‘tools’ om een plotselinge uitbraak in kaart te brengen, waaronder de epidemische curve, het cohortonderzoek en het patiënt-controleonderzoek. Op het einde van het hoofdstuk wordt een stappenplan gegeven voor onderzoek naar plotselinge uitbraken.


title: SARS Coronavirus and Lung Fibrosis

text: Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A novel coronavirus (SARS-CoV) has been shown to be the causative agent of SARS. The typical clinical feature associated with SARS is diffuse alveolar damage in lung, and lung fibrosis is evident in patients who died from this disease. The mechanisms by which SARS-CoV infection causes lung fibrosis are not fully understood, but transforming growth factor-β (TGF-β) and angiotensin-converting enzyme 2 (ACE2)-mediated lung fibrosis are among the most documented ones. The activation of the TGF-β/Smad pathway is critical to lung fibrosis. SARS-CoV infection not only enhances the expression of TGF-β, but also facilitates its signaling activity. The SARS-CoV receptor ACE2 is a negative regulator of lung fibrosis, and SARS-CoV infection decreases ACE2 expression. Therefore, SARS-CoV infection may lead to lung fibrosis through multiple signaling pathways and TGF-β activation is one of the major contributors.


title: Infektionsverlauf und Pathogenität

text: Die Ausbreitung eines Virus im Organismus ist je nach Virus verschieden. Es gibt akute, persistierende und latente Virusinfektionen. Die pathogenen Eigenschaften eines Virus können bedingt sein durch direkt vom Virus ausgelöste Schäden in den infizierten Zellen und indirekt durch die Auswirkungen der Immunantwort auf die Virusinfektion. Bei erstmaligem Kontakt mit einem Virus lösen Mechanismen der angeborenen Immunität (Basisabwehr) eine Entzündung aus, welche die adaptive Immunität anregt; gemeinsam blockieren sie die weitere Replikation und Ausbreitung. Bei einer Zweitinfektion reagiert die adaptive Immunität blitzschnell (»Gedächtnis«) fast ohne Entzündungen. Polymorphismen des Wirtes oder des Virus beeinflussen den Ablauf der Infektion.


Arterivirus(‡): Arteriviridae


title: Biologische Bedrohung

text: In diesem Kapitel wird auf die Besonderheiten von Krankheitserregern eingegangen, die besonders im Bereich der sog. Ersthelfer/»First Responder« sowohl auf militärischer als auch ziviler Seite zu beachten sind. Nicht nur die zunehmenden Resistenzen der Erreger gegenüber Therapeutika, sondern auch das Auftreten neuer bzw. bereits zurückgedrängter oder ausgerotteter Infektionskrankheiten (z. B. »Polio«) werden regelmäßig beobachtet. Sofern es sich dabei um gefährliche, d. h. lebensbedrohliche, hoch ansteckende Infektionskrankheiten handelt, kommen diese vorwiegend in sog. Entwicklungsländern in sub- und tropischen Gebieten vor. Sie können aber auch über den internationalen Reise- und Handelsverkehr importiert werden. Darüber hinaus könnten die Erreger solcher Infektionskrankheiten möglicherweise von kriminellen bzw. terroristischen Gruppierungen für Anschläge als biologische Waffen missbraucht werden.


title: Signaling Pathways of SARS-CoV In Vitro and In Vivo

text: Severe acute respiratory syndrome (SARS) is a respiratory illness with variable symptoms that was recognized as the first near-pandemic infectious disease of the twenty-first century. A novel human coronavirus, named SARS coronavirus (SARS-CoV), derived from SARS patients was reported as the etiologic agent of SARS. Studying the signaling pathways of SARS-infected cells is key to understanding the molecular mechanism of SARS viral infection. Cell death is observed in cultured Vero E6 cells after SARS-CoV infection. From SARS-CoV infection to cell death, p38 mitogen-activated protein kinase (MAPK) is a key participant in the determination of cell death and survival. Two signaling pathways comprising signal transducer and activator of transcription 3 (STAT3) and p90 ribosomal S6 kinase (p90RSK) are downstream of p38 MAPK. AKT and JNK (Jun NH(2)-terminal kinase) signaling pathways are important to establish persistent infection of SARS-CoV in Vero E6 cells. Expression studies of SARS-CoV proteins indicate that the viral proteins are able to activate signaling pathways of host cells. The study of signaling pathways in SARS-CoV patients is difficult to perform compared with in vitro studies due to the effects of the human immune system. This review highlights recent progress in characterizing signal transduction pathways in SARS-CoV-infected cells in vitro and in vivo.


title: Infektionen des ZNS

text: Viren, Bakterien, Protozoen, Helminthen und Pilze können, sofern es ihnen gelingt, die Blut-Hirn-Schranke zu überwinden, ZNS und gelegentlich das periphere Nervensystem involvieren; Meningitis, Enzephalitis, Hirnabszess, Meningovaskulitis oder granulomatöse Prozesse sind potenzielle Folgen.


docid: fidpskcs

title: Invasive Aspergillosis in the Intensive Care Unit: Beyond the Typical Haematological Patient

text: Data about incidence of invasive aspergillosis in intensive care units (ICU) are scarce and variable. Incidences ranging from 2 to 24% have been reported, which might reflect different autopsy policies amongst centres. Recent studies have shown that many patients with invasive aspergillosis do not have a haematological diagnosis. Instead, conditions such as chronic obstructive pulmonary disease and liver failure became recognized as important risk factors. The diagnosis remains difficult in these patients, since diagnostic tests have not been widely validated outside the haematological boundaries. Mechanical ventilation precludes the interpretation of clinical signs and radiological diagnosis is clouded by underlying lung pathology. Respiratory cultures lack sensitivity and specificity. At the moment, diagnosis is best made by testing for galactomannan in bronchoalveolar fluid samples (sensitivity and specificity of > 87%). Testing galactomannan in sera has limited sensitivity for the non-neutropenic. Modern diagnostic tests such as PCR and beta-glucan have never been validated in an ICU population. Due mostly to major delays in the diagnosis, mortality exceeds 50%. Although our therapeutic armamentarium against invasive aspergillosis has improved in recent years, data concerning safety and efficacy of new antifungal agents in the ICU setting are lacking.


docid: wdlrtsjv

title: Plague in the 21st Century: Global Public Health Challenges and Goals

text: Yersinia pestis, the Gram-negative bacterial agent of plague, is a zoonotic pathogen that primarily infects wild rodents and is transmitted by fleas. Y. pestis is one of the most invasive and virulent bacterial pathogens and has caused devastating pandemics, including the Black Death of 14th century Europe. The last plague pandemic began in Asia in the last half of the 19th century and lingered well into the 20th century, causing tens of millions of deaths as it spread across the world.


title: Molecular and Biochemical Characterization of the SARS-CoV Accessory Proteins ORF8a, ORF8b and ORF8ab

text: A novel coronavirus was identified as the aetiological agent for the global outbreak of severe acute respiratory syndrome (SARS) at the beginning of the twenty-first century. The SARS coronavirus genome encodes for proteins that are common to all members of the coronavirus, i.e. replicase polyproteins (pp1a and pp1b) and structural proteins (spike, membrane, nucleocapsid and envelope), as well as eight accessory proteins. The accessory proteins have been designated as open reading frames (ORF) 3a, 3b, 6, 7a, 7b, 8a, 8b and 9b, and they do not show significant homology to viral proteins of other known coronaviruses. Epidemiological studies have revealed that the part of the viral genome that encodes for ORF8a and ORF8b showed major variations and the animal isolates contain an additional 29-nucleotide sequence which is absent in most of the human isolates. As a result, ORF8a and ORF8b in the human isolates become one ORF, termed ORF8ab. In this chapter, we will discuss the genetic variation in the ORF8 region, expression of ORF8a, ORF8b and ORF8ab during infection, cellular localization and posttranslational modification of ORF8a, ORF8b and ORF8ab, participation of ORF8a, ORF8b and ORF8ab in viral–viral interactions, their effects on other viral proteins and impact on viral replication and/or pathogenesis.


docid: rkxmeyqt

title: Lead Discovery Using Virtual Screening

text: The practice of virtual screening (VS) to identify chemical leads to known or novel targets is becoming a core function of the computational chemist within industry. By employing a range of techniques, when attempting to identify compounds with activity against a biological target, a small focused subset of a larger collection of compounds can be identified and tested, often with results much better than selecting a similar number of compounds at random. We will review the key methods available, their relative success, and provide practical insights into best practices and key gaps. We will also argue that the capability of VS methods has grown to a point where fuller integration with experimental methods, including HTS, could increase the effectiveness of both.


title: Molekularbiologische Testungen

text: In keinem anderen Bereich der Medizin gehören molekularbiologische Testungen inzwischen so sehr zum diagnostischen Standardrepertoire wie im Bereich der Infektionsdiagnostik. Für den direkten Erregernachweis haben sich hauptsächlich zwei Methoden durchgesetzt, die Polymerasekettenreaktion und die Immunchromatographie, die häufig in Form von Teststreifen oder Testkarten angeboten wird. Vorteilhaft an der Polymerasekettenreaktion ist insbesondere die Möglichkeit, neben dem Erregernachweis die Simultananalyse von Resistenzdeterminanten oder Virulenzfaktoren einzubinden. Im Zeitalter der multiresistenten (Krankenhaus-)Keime gewinnt die schnelle und zuverlässige molekularbiologische Differenzierung vor den Hintergrund einer unmittelbaren Einleitung von möglichst frühzeitigen und damit auch effizienten Isolierungsmaßnahmen von betroffenen Patienten zunehmend an Bedeutung.


title: Pädiatrische Transfusionsmedizin

text: Die pädiatrische Transfusionsmedizin unterscheidet sich durch Erkrankungen, die auf besondere Blutgruppeninkompatibilitäten zwischen Mutter und Fetus zurückzuführen sind, sowie durch die altersabhängig unterschiedlichen Blutvolumina und Transfusionsgrenzen wesentlich von der Transfusionsmedizin im Erwachsenenalter.


title: The Use of Retroviral Pseudotypes for the Measurement of Antibody Responses to SARS Coronavirus

text: Neutralization assays allow for sensitive detection of functional antibody responses directed against the surface protein envelopes of many viruses. For high-containment viruses like SARS coronavirus (CoV), however, these assays are not widely applicable due to the requirement for high biosafety laboratory facilities and specially trained personnel. In order to effectively address this containment issue, retroviral pseudotypes have been used as surrogates of the live virus for neutralization assays. The pseudotype-based neutralization assay system is highly flexible, allowing for a choice of reporter systems, and is readily adaptable to newly emerging virus strains.


title: Asthma: Pathophysiology and Diagnosis

text: Although asthma is a common disorder affecting approximately 7.8% of the United States population (Schiller et al. 2006) or 23 million Americans, the pathogenesis of this disease remains to be fully elucidated. Extensive research over the last few decades has yielded a better understanding of asthma. We know that the basic features of asthma include episodic airways inflammation, airways hyperresponsiveness, and mucous hypersecretion. Although we understand the basic clinical features of asthma, the links between symptoms, physical signs, and underlying pathophysiological mechanisms are still being delineated. Asthma is a heterogeneous disease process with varying phenotypes and presentations. In this chapter, we will briefly explore some major theories of asthma pathogenesis, both new and old. We will also explore how understanding the pathophysiology of asthma can help us to understand the symptoms and presentation of asthma, as well as the best strategies for diagnosing this disease.


Rituximab-related Severe Toxicity


docid: chmktbvl

title: Quaternary Structure of the SARS Coronavirus Main Protease

text: The maturation of the SARS coronavirus (CoV) involves the autocleavage of polyproteins 1a and 1ab by a main protease and papain-like protease. The functional unit of the main protease is a dimer in which each subunit has a Cys145–His41 catalytic dyad, with His41 acting as a general base. There is also a close correlation between dimer formation and the enzyme catalytic activity. A flip-flop mechanism is proposed for the main protease, in which the two subunits are used alternately in acylation and deacylation. Both the main protease and the papain-like protease are ideal targets for rational drug design strategies against SARS-CoV.


title: Influence of Postoperative Enteral Nutrition on Cellular Immunity: Investigative Procedures, Tests and Analysis

text: “Postoperative enteral nutrition and cellular immunity” is mostly described in the literature on research into surgical complications. The intention is to show whether a given treatment can be identified as having a beneficial clinical effect and to demonstrate this by the effect on, among other factors, cellular immunity. In order to show that the inclusion of a particular nutrient would have a beneficial effect on cellular immunity, and thus the postoperative course, the research is often related to various types of postoperative immuno-nutrition. This chapter will briefly describe various types of immuno-nutrition and the influence of the added nutrients on cellular immunity. In describing cellular immunity, many different lymphocyte subpopulations have been used, along with markers to describe their activity. As all the different subpopulations can be difficult to remember and understand, the aim of this chapter is to give the reader a short overview of the cellular immunity aspects. It will also give a brief overview of the two types of cells most often described in the literature and their function in the immune response. Many articles indicate the subpopulations of different lymphocyte groups in percentages, making it difficult to understand the comparisons between the different phases of, for example, a postoperative course. This chapter will provide a summary of the investigative procedures described in the literature and explain how to proceed with tests and analyses and how to specify the results so that they can be used to compare the results obtained at different times during the test period. A brief description of the flow cytometric method has therefore been included to give the reader an understanding of how the number of subpopulation percentages is indicated.


docid: etkhrgxp

title: Malaria in Women and Children

text: After reading this chapter and answering the discussion questions that follow, you should be able to: Explain the global burden of malaria, discuss its clinical manifestations, and appraise its health impact on women and children. Analyze the mechanisms and consequences of malaria and HIV co-infection and discuss current treatment, control and prevention strategies. Describe the challenges posed by vector resistance to insecticides, parasite resistance to antimalarials, climate change, wars/conflicts, and HIV/AIDS to malaria control and prevention efforts. Evaluate social, cultural, and economic limitations of community-based programs for malaria control and prevention.


title: Miscellaneous Enteric Viruses

text: Acute viral gastroenteritis is second only to the common cold as a cause of illness in the United States. It often occurs in outbreaks, sometimes associated with food or water, and is a major recurrent problem in public health. Although most infections are self-limited, viral gastroenteritis can cause severe dehydration (particularly rotavirus), as well as chronic diarrhea in children with immunodeficiency syndromes such as severe combined immunodeficiency. Enteric viral infections are also a significant cause of diarrhea in patients with AIDS. Similar to adenovirus, rotavirus and enterovirus are associated with intussusception in children.


title: Cellular Entry of the SARS Coronavirus: Implications for Transmission, Pathogenicity and Antiviral Strategies

text: A novel coronavirus was identified as the causative agent of the lung disease severe acute respiratory syndrome (SARS). The outbreak of SARS in 2002/2003 was associated with high morbidity and mortality and sparked international research efforts to develop antiviral strategies. Many of these efforts focussed on the viral surface protein spike (S), which facilitates the first indispensable step in the viral replication cycle, infectious entry into target cells. For infectious cellular entry to occur, the S protein must engage a cellular receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). The interface between ACE2 and S protein, which has been characterized at the structural level, constitutes a key target for vaccines and inhibitors, and is believed to be an important determinant of viral pathogenesis and interspecies transmission. In this chapter, we will discuss how SARS-S mediates cellular entry and we will review the implications of this process for SARS coronavirus (SARS-CoV) transmission, disease development and antiviral intervention.


docid: gxyvkzkv

title: Public Health Surveillance

text: The term surveillance, derived from the French word meaning “to watch over,” may be defined as a system providing close observation of all aspects of the occurrence and distribution of a given disease through the systematic collection, tabulation, analysis, and dissemination of all relevant data pertaining to that disease.(1) The preferred term is public health surveillance, which emphasizes the focus of surveillance as discussed in this chapter to develop data that results in a public health preventive act ion. This distinguishes public health surveillance from other types of surveillance.(2) Although the methodology of surveillance is basically descriptive, its function is more than merely collective and archival. Surveillance must be dynamic, current, purposeful, and result in a public health action. This action frequently results in the establishment of a new or the reinforcement of an existing public health policy. It is fundamental for the prompt and effective control and prevention of disease. Traditionally, surveillance was first applied to the acute communicable diseases in the mid-1800s.(3) Since then, surveillance methodologies have been utilized to cover a many infectious diseases,(1) a wide variety of non-infectious diseases, and other health-related events such as environmental hazards, potential bioterrorism events injuries, vaccinations, the distribution of biological products, and health-care delivery.


title: Structural Molecular Insights into SARS Coronavirus Cellular Attachment, Entry and Morphogenesis

text: Coronavirus spikes have the largest mass of any known viral spike molecule. The spike is a type 1 viral fusion protein, a class of trimeric surface glycoprotein proteins from diverse viral families that share many common structural and functional characteristics. Fusion proteins are mainly responsible for host cell receptor recognition and subsequent membrane fusion, and may perform other roles such as virus assembly and release via budding. The conformational changes that occur in the spike of intact SARS coronavirus (SARS-CoV) when it binds to the viral receptor, angiotensin-converting enzyme 2 (ACE2) are described. Clues to the structural/functional relationships of membrane fusion have been made possible by the development of viral purification and inactivation methods, along with cryo-electron microscopy (cryo-EM) and three-dimensional (3D) image processing of many different images containing multiple views of the spikes. These methods have allowed study of the spikes while still attached to virions that are noninfectious, but fusionally competent. The receptor-binding and fusion core domains within the SARS-CoV spike have been precisely localized within the spike. Receptor binding results in structural changes that have been observed in the spike molecule, and these appear to be the initial step in viral membrane fusion. A working model for the stepwise process of receptor binding, and subsequent membrane fusion in SARS-CoV is presented. Uniquely, the large size of the SARS-CoV spike allows structural changes to be observed by cryo-EM in the native state. This provides a useful model for studying the basic process of membrane fusion in general, which forms an essential part of the function of many cellular processes.


title: Infectious Disease Epidemiology

text: Most textbooks dealing with the epidemiology of infectious diseases address the epidemiological features (also named biology) of specific infectious diseases. In this chapter, the focus is placed on the concepts and methods more specific to the general epidemiological study of infectious diseases. At a later stage, implementation of these methods must be adapted to the specific infectious disease under consideration. Then, detailed knowledge of the disease biology is of capital importance.


title: Polyunsaturated Fatty Acids and Cytokines: Their Relationship in Acute Lung Injury

text: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory diseases whose clinical severity depends on the grade of inflammatory response. Inflammatory cytokines are key elements in the pathogenesis of ALI/ARDS, and the occurrence of an imbalance between pro- and anti-inflammatory cytokines leads to additional non-pulmonary organ dysfunction which contributes to excess mortality rates. Treatment of these patients includes nutrition support with lipids, usually soybean oil-based lipid emulsions, which are rich in omega (n)-6 polyunsaturated fatty acids (PUFAs) and deficient in n-3 PUFAs; however, too much n-6 PUFAs are detrimental due to their pro-inflammatory effects. Conversely, a large amount of experimental studies and some randomized clinical trials showed the benefits of the n-3 PUFA administration in the context of ALI because of their anti-inflammatory properties. Based on these data, several scientific societies recommended in their guidelines, with an A or B grade of recommendation, the use of n-3 PUFAs in ALI/ARDS patients. However, at present, the issue of lipid therapy in ALI/ARDS is still controversial due, at least in part, to inconclusive or contradicting results in several recent clinical trials using n-3 PUFAs.


title: Mathematical Modeling of UV Disinfection

text: Mathematical modeling of the UV disinfection process provides a basis for sizing ultraviolet disinfection equipment and for interpreting test results. It also allows for adaptation of UV systems to specific disinfection processes and for the disinfection of specific microorganisms. Disinfection is generally modeled in terms of the survival, or its converse the inactivation rate, and may be rendered as a fraction or a percentage. Disinfection is invariably a logarithmic process, as is microbial growth. The disinfection rate of the microorganisms varies widely and is subject to many complexities, including shoulder effects, second stage decay, relative humidity effects, and photoreactivation. Not all these processes need be considered for every design application, but a familiarity with these effects is essential for understanding UV disinfection. Furthermore, not all of these processes can be completely and accurately modeled at present, but enough is known to adequately design reliable UV disinfection systems. All of these processes can be modeled with basic exponential equations and by using computational methods if necessary. For more detailed background information on theoretical decay models for general disinfection purposes see Kowalski (2006), Chick et al. (1963), or Hiatt (1964).


title: Health Care Facilities

text: This chapter addresses applications of ultraviolet germicidal irradiation (UVGI) in health care facilities, including laboratories and animal or veterinary facilities. This chapter does not review the applicable guidelines or standards for air quality in these facilities, which typically do not mention UVGI, but the references and Chapter 11 may be consulted for more detailed information. The types of UV systems covered in this chapter have been addressed in detail in previous chapters and these designs are not revisited here. Instead, this chapter discusses the various applications of UV to the indicated facilities, how they have been applied in the past, what effectiveness they have previously demonstrated, and how new UV systems may be applied to reduce the microbiological hazards associated with each type of facility. Also addressed here are the types of pathogens that are unique to certain facilities and, in particular, nosocomial pathogens and the problem of increasing drug resistance.


title: Pulmonary Infections: Pneumonia

text: The different appearances of pneumonia such as ill-defined nodules, ground-glass opacities, and consolidations can be easily detected and differentiated with MRI. Since very small nodules and calcifications are extremely challenging due to rather thick slices and loss of signal, MRI is highly recommended as a follow-up tool, to avoid repetitive investigations using ionizing radiation. With the sensitivity of T2-weighted sequences and the potential of contrast-enhanced T1-weighted sequences, important differential diagnostic considerations can be provided. Additionally, developing complications, such as pericardial or pleural effusions, empyema or lung abscess, are easily recognized. Current and future studies are to demonstrate that MRI is well suited as a monitoring and follow-up tool during and after therapy and compares favorably with CT or other imaging methods regarding sensitivity and specificity.


title: Nanomechanical Cantilever Array Sensors

text: In recent years, mechanics has experienced a revival, as microfabrication technologies and nanotechnology are applied to produce tiny structures. The development of ultraprecise position sensing started three decades ago with a novel imaging technique called atomic force microscopy, which provides ultrahigh topography resolution on the atomic scale by raster-scanning the surface with a microfabricated cantilever beam that has a tiny tip at its free end. The high force sensitivity can not only be used for imaging, but also allows the measurement of surface forces during molecule adsorption processes on the cantilever surface, thus enabling cantilevers to act as chemical sensors. Because of their small size, cantilevers allow fast and reliable detection of small concentrations of molecules in air and solution. In addition to artificial nose and label-free biosensing applications, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy and monitoring of chemical reactions. In the past few years, the cantilever-sensor concept has been extended to medical applications and has entered clinics for pilot studies on patients. The small size and scalability of cantilever array sensors might turn out to be advantageous for diagnostic screening applications and disease monitoring, as well as for genomics or proteomics. Using microcantilever arrays allows simultaneous detection of several analytes and solves the inherent problem of thermal drifts often present when using single microcantilever sensors, as some of the cantilevers can be used as sensor cantilevers for detection, and others as passivated reference cantilevers that do not show affinity to the molecules to be detected.


title: Disrupted Odor Perception

text: Olfactory loss is frequent. However, in public not many people complain of that, or they are even not (fully) aware of it. This indicates that it is possible to live a life without a sense of smell, albeit it is more dangerous, less pleasant, and food tastes much less interesting. Most common causes for smell loss are sinunasal disease (chronic rhinosinusitis with and without nasal polyps), acute infections of the upper airways, head trauma, and neurodegenerative disorders. In many people smell loss seems to be due to the aging process. Before treatment olfactory disorders are diagnosed according to cause with the medical history being a big portion of the diagnostic process. Olfactory disorders are in principle reversible, with a relatively high degree of spontaneous improvement in olfactory loss following infections of the upper respiratory tract. Medical treatment is according to cause. It also involves surgical approaches as well as conservative treatments including the use of corticosteroids, antibiotics, or smell training. Because today olfactory dysfunction seems to receive more attention than in previous years it can be expected that tomorrow we will have more specific and effective treatment options available.


title: After the storm

text: Discussion of the encephalitis problem has not lost its vigor, even after the passing of the great wave of epidemic encephalitis. The occurrence of encephalitic syndromes has repeatedly necessitated considering the relationships between the individual diseases. Such discussions were necessarily based largely upon comparative disease research, as the experimental–biological elucidation of epidemic encephalitis remains in the dark. Epidemiology, clinical manifestations, course, and anatomic substrate have nonetheless revealed quite specific characteristics that have enabled its differentiation from other frequently occurring encephalitic syndromes Gerhard Döring, 1941


title: Epidemiological Concepts

text: Epidemiology is the study of the distribution and determinants of health-related states, conditions, or events in specified populations and the application of the results of this study to the control of health problems.(1) It is a quantitative science concerned in infectious diseases with the circumstances under which disease processes occur, the factors that affect their incidence and the host response to the infectious agent, and the use of this knowledge for control and prevention.(2) It includes the pathogenesis of disease in both the community and the individual. For infectious diseases, one must study the circumstances under which both infection and disease occur, for these may be different. Infection is the consequence of an encounter of a potentially pathogenic microorganism with a susceptible human host through an appropriate portal of entry and usually involves a demonstrable host response to the agent. Exposure is the key factor, and the sources of infection lie mostly outside the individual human host, within the environment, or in other infected hosts. Disease represents one of the possible consequences of infection, and the factors important in its development are mostly intrinsic to the host, although the dosage and virulence of the infecting microbe play a role. These intrinsic factors include the age at the time of infection, the portal of entry, the presence or absence of immunity, the vigor of the primary defense system, the efficiency and nature of humoral and cell-mediated immune responses, the genetic makeup of the host, the state of nutrition, the presence of other diseases, and psychosocial influences. These factors that result in the occurrence of clinical illness among those infected have been called the “clinical illness-promotion factors,”(3) and many of them remain unknown. The host responses can include death, the classic clinical features of the disease, mild or atypical forms, subclinical and inapparent infections, and the carrier state, which may exist in the absence of a detectable host response. While the clinician is primarily concerned with disease, the epidemiologist is interested in both infection and disease. Infection without disease is a common phenomenon, so that a study limited to clinical illness alone would give an incomplete epidemiological picture and would be a poor basis for control and prevention.(4) A full understanding involves the pathogenesis of the process leading to clinical disease both in the community and in the individual.


title: Infektionskrankheiten

text: Erreger: Morbilli-Virus, ein RNA-Virus aus der Familie der Paramyxoviren. Epidemiologie: Verbreitung weltweit. Durchseuchungsgrad früher sehr hoch, seit Einführung der Schutzimpfung in westlichen Ländern stark rückläufig. Am häufigsten erkranken Kinder im Vorschulalter. Ansteckungsmodus: Tröpfcheninfektion. Kontagiosität: 2 Tage vor Symptombeginn bis 4 Tage nach Auftreten des Exanthems.


title: Excessive Exercise and Immunity: The J-Shaped Curve

text: Exercise modulates the innate and specific arms of the immune system with a marked intensity-dependent response. This response might be influenced by sex differences and other factors including age, nutrition status, and overall level of psychological stress. Exercise immunology is the field that studies this area. In the 1990s, Dr. Nieman formulated the controversial “J-shaped hypothesis” to describe the relationship between exercise intensity and the risk of acquiring upper respiratory tract infections (URTI). This hypothesis suggests that moderate exercise has the ability to improve immune function above sedentary levels while high intensity exercise depresses the immune system. However, some methodological problems exist in studies of the J-curve which makes evidence more anecdotal than evidence-based regarding the role of moderate and intense exercise in the incidence of URTI. These limitations are presented in the chapter.


title: Structural Biology and the Design of Effective Vaccines for HIV-1 and Other Viruses

text: Structural biology provides a wealth of information about the three-dimensional organization and chemical makeup of proteins. An understanding of atomic-level structure offers enormous potential to design rationally proteins that stimulate specific immune responses. Yet current vaccine development efforts makes little use of structural information. At the Vaccine Research Center, a major goal is to apply structural techniques to vaccine design for challenging pathogens, that include human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses such as influenza, Ebola, and respiratory syncytial viruses. Our three-part strategy involves 1.) the definition of the functional viral spike at the atomic level 2.) achieving a structural understanding of how neutralizing antibodies recognize the spike, and 3.) rational development of proteins that can elicit a specific antibody response. Overall, our strategy aims to incorporate information about viral spike-antibody interactions, to assimilate immunogenic feedback, and to leverage recent advances in immunofocusing and computational biology.


title: Krankheiten der Atmungsorgane

text: In der Nase wird die Atemluft: - gereinigt (Filterwirkung der Nasenhaare, Partikelniederschlag auf dem Nasenschleim, rachenwärts gerichtete Zilienbewegung des Epithels) - erwärmt (fast bis auf Körpertemperatur) - befeuchtet (nahezu vollständige Sättigung mit Wasserdampf) Gestörte Nasenatmung kann daher Reizung und Austrocknung der Bronchialschleimhaut bewirken. Dem ist bei künstlicher Beatmung (Trachealkatheter, Trachealkanüle) Rechnung zu tragen.


title: Effectiveness of Social Networks for Studying Biological Agents and Identifying Cancer Biomarkers

text: Social networks form phenomena that exist and evolve; they are dynamic. These phenomena have been realized and studied by the anthropology and sociology research communities since 1930. However, the recent rapid development in information technology and the internet has increased the interest in social networks and as a model they have been adapted to more applications and domains. Though researchers first studied social networks of humans, for our study described in this chapter we argue that genes and proteins act collaboratively and exist in communities analogous to humans, animals, insects, etc. They complement each other and collectively achieve specific tasks where some would have major roles appearing upfront and others may play minor background roles. However, molecules turn into aggressive actors when their internal structure is augmented; consequently, they may deviate from their target, change camp, and disturb other molecules leading to disaster. Such mutations may be uncontrolled and unintentionally occur inside a body, or they may be intentional and controlled by humans to serve one of two purposes, treatment or bioterrorism. In other words, mutation in the molecules (genes) can lead to a change in behavior. This may lead to good or bad effect, e.g., recovery from illness or diseases that may severely affect the body causing disability or death. Once mutated outside the body, molecules may turn into harmful biological weapons of mass destruction. The latter process does not require sophisticated equipment and hence is extremely dangerous with the uprising global terrorism activities. Bioterrorism is therefore a serious concern for humanity. One could say that mutated biological agents outside the body once misused could be way more dangerous than mutated molecules within the body. In this chapter, we will elaborate on bioterrorism and its consequences; we will also propose a model to study social networks of genes within the body leading to the identification of disease biomarkers.


title: Neonatologie

text: Durch die Fortschritte der Perinatalmedizin ist die neonatale Mortalität (Anzahl der in den ersten 28 Lebenstagen verstorbenen Neugeborenen pro 1.000 Lebendgeborene) in Deutschland zwischen 1970 und 1991 von 17 auf 4/1.000 gesunken und seither auf diesem geringen Niveau stabil. Ungefähr 6,5% aller Geburten erfolgen vor der vollendeten 37. Schwangerschaftswoche; etwa 1,5% der Kinder sind sehr kleine Frühgeborene (Geburtsgewicht <1.500 g, Gestationsalter <32 vollendete Gestationswochen). Die Unreife von Organsystemen und -funktionen können bei sehr unreifen Frühgeborenen postnatal zu einer Reihe von akuten Erkrankungen und chronischen pulmonalen und neurologischen Folgeschäden führen: Atemnotsyndrom, bronchopulmonale Dysplasie, intrazerebrale Blutung, periventrikuläre Leukomalazie, persistierender Ductus arteriosus, Apnoe, Bradykardie, nekrotisierende Enterokolitis, nosokomiale Sepsis, Frühgeborenenretinopathie und psychomotorische Retardierung. Die Frühgeburtlichkeit trägt als wesentlicher Faktor zur peri- und neonatalen Sterblichkeit bei.


title: Inhibitors of Hydrolases with an Acyl–Enzyme Intermediate

text: Peptidases and esterases are hydrolytic enzymes; 2–3% of all gene products are assigned to this group alone. They are therefore, an important group of target proteins for the design of new medicines and have a special importance for structure-based drug design. This is reflected in the fact that about 14% of all known human peptidases are presently being investigated as possible target structures for drug therapy.


title: Krankheiten des Herz-Kreislauf-Systems

text: Die Pumpleistung des Herzens nimmt mit steigendem venösem Zufluss durch folgende Mechanismen automatisch zu: - Frank-Starlin-Mechanismus: Vergrößerung des venösen Angebotes → stärkere diastolische Kammerfüllung unter Zunahme der Faserdehnung → Steigerung der Kontraktionskraft und des Schlagvolumens. - Mechanische Steigerung der Herzfrequenz: Stärkere Füllung des rechten Vorhofes → Stimulation des Sinusknotens durch Dehnung → Anstieg der Schlagfrequenz (mit frequenzbedingter Kontraktilitätssteigerung).


Threatwatch


Discussion


Events calendar


title: Belief reversals as phase transitions and economic fragility: a complexity theory of financial cycles with reflexive agents

text: This paper aims to contribute to the analysis of expectations and belief reversals in a evolutionary and complexity economics framework. It formulates its analysis in terms of the concept of reflexivity, drawing on the ideas regarding reflexivity in financial markets of George Soros, and lays out a model of how a financial cycle expresses a systematic pattern of interacting feedback effects. The paper develops this analysis as a complex interaction between sets of heterogeneous expectations derived from the behavior of reflexive economic agents. Positive and negative feedback phases in a cycle are distinguished and associated with boom and bust stages of that cycle. A central role is played by agents’ beliefs and judgments underlying their expectations, and how those beliefs and judgments in uncertain circumstances are changeable and subject to abrupt reversals which can manifest themselves in “Minsky moments.” The paper argues that agents’ belief reversals result from their misconceptions about causal processes in booms and upswings, a misconception that reflects their tendency to think causally in terms of negative feedback patterns rather than positive ones.


May 2020 People & Events


title: Discovery and Preclinical Work

text: In any drug discovery and development effort, we must accomplish a number of critical steps to arrive at a compound that is safe and efficacious, and also exhibits the complex array of desired drug-like behaviors that warrants advancement to the clinic. These tasks include target identification and validation; screening for active compounds; chemical modification of candidate compounds to achieve optimized pharmacology; formulating the final drug product; and establishing safety in preclinical models. “Repurposing” drugs that have previously been approved (or shown to be safe in humans) for new clinical indications can provide a faster, less risky, and more cost-effective route for bringing a new therapy to patients. Such shortcuts in development can be particularly valuable to resource-constrained academicians. When performing drug discovery research, we must be particularly attentive to the robustness of our experiments, because inability to reproduce academic data continues to be a sticking point when projects are transferred to industry. Our experiments must be appropriately blinded, statistically powered, and meticulously documented so that our findings are worthy of the large investment required for their further translation into a drug. This chapter walks through the essential preclinical drug development steps that lead to a clinical drug candidate.


title: Broader Considerations of Medical and Dental Data Integration

text: Dental health insurance coverage in the United States is either nonexistent (Medicare and the uninsured), spotty (Medicaid) and limited (most employer-based private benefit plans). Perhaps as a result, dental health in the United States is not good. What public policy makers may not appreciate is that this may well be impacting medical care costs in a way that improved dental benefits would produce a substantial return to investment in expanded dental insurance coverage.


title: Besondere Patientengruppen im Intensivtransport

text: Neben den im vorangegangenen Kapitel besprochenen Krankheitsbildern gibt es im Rahmen der Durchführung eines Intensivtransportes Patienten, die nicht „krank“ im eigentlichen Sinne sind, jedoch aufgrund spezieller Entwicklungs-, Krankheits- oder Therapieverläufe einer besonderen Aufmerksamkeit bedürfen. Hierzu zählen normale Früh- und Neugeborene, Neugeborene mit angeborenen Herzfehlern oder Lungenversagen, und ebenso Patienten, bei denen eine Infektion mit therapieresistenten Erregern besteht.


title: Infektiologie

text: Die Infektiologie ist gerade innerhalb der Pädiatrie von elementarer Bedeutung, zumal Kinder innerhalb der ersten Jahre als Folge häufiger Erregerexposition an zahlreichen Infektionen erkranken. In den meisten Fällen handelt es sich um selbstlimitierende, virale Infektionen, vorwiegend der Atemwege oder des Gastrointestinaltrakts. Trotzdem werden gerade auch bei Atemwegsinfektionen wie z. B. der Tonsillopharyngitis oder der Otitis media oftmals Antibiotika verschrieben. Deshalb sind Kenntnisse über die Ätiologie und optimierte diagnostische Algorithmen sinnvoll, um Patienten eine adäquate Therapie zuführen zu können. Demgegenüber steht die Erkennung und Behandlung schwerer, potenziell lebensbedrohlicher Infektionserkrankungen, wie z. B. HIV-Infektion. Der didaktische Zugang zur Infektionsmedizin bietet verschiedene Ansatzpunkte. Für einige Erkrankungen wählen wir die Kategorisierung in Abhängigkeit vom betroffenen Organsystem, für andere wiederum den erregerspezifischen Ansatz. Zum Teil werden organspezifische Infektionskrankheiten in den jeweiligen Kapiteln abgehandelt. In einem kürzeren Kapitel widmen wir uns Pilzen und Parasiten. Hiernach folgt ein differenzialdiagnostischer Zugang zum Patienten nach Tropenreise. Abschließend folgt ein kurzer Überblick zum Thema Impfungen.


title: Motive für große Personalabbaupläne, der Verlust von Humankapital und Börsenreaktionen – Eine Analyse der globalen Luftfahrtindustrie

text: The present study focusses on the controversial issues between human resource management and international capital markets. It analyzes the impact of layoff announcements on the market value of the global airline sector while utilizing the event study methodology. Between 2003 and 2012, 84 redundancy plans were announced by 22 airlines. The empirical evidence underlines that there is no generalization of the capital market’s reaction to these announcements; it is rather the very specific layoff motive that drives the market perception. In particular, proactive measures with a focus on restructuring show a positive impact on the shareholder value.


title: Virale Infektionen: RNA-Viren

text: Rhinoviren sind die Haupterreger der sog. Erkältungskrankheiten. Eine wichtige Rolle spielen sie auch als Auslöser von Asthmaattacken. Es findet eine stete Kozirkulation mehrerer Serotypen statt, im gemäßigten Klima gibt es Herbst-, Winter- und Frühjahrsepidemien, die Übertragung geschieht weit häufiger über infizierte Sekrete als durch Aerosole. Rhinoviren gehören zu den Picornaviren. Rhinoviren sind sehr kleine Viren mit einem positiven Einzelstrang-RNA-Genom ohne Lipidhülle und daher gegen Detergens enthaltende Desinfektionsmittel sehr resistent. Sie sind empfindlich gegen Umgebungs-pH außerhalb des Bereichs 5,0–7,5. Zurzeit bilden sie zusammen mit den Enteroviren das Genus Enterovirus der Picornaviren. Serologisch lassen sich über 100 Typen unterscheiden. Kennzeichnend ist die Bindungsfähigkeit an das von den meisten Rhinoviren für die Zelladsorption genützte ICAM-1 (interzelluläres Adhäsionsmolekül). Nach einer Inkubationszeit von 1–3 Tagen tritt Schnupfen auf, die höchste Viruskonzentration im Nasensekret nach 2–4 Tagen, wiederum nach 2–4 Tagen bei disponierten Patienten auch bronchiale Obstruktion. Es konnte gezeigt werden, dass zu dieser Zeit auch Virus-RNA im Bronchialepithel vorhanden ist. Die postinfektiöse bronchiale Hyperreagibilität korreliert mit der Dauer des Virus-RNA-Nachweises im Nasopharynx. Die Immunität ist im Wesentlichen abhängig von der nur sehr kurzen Anwesenheit sekretorischer spezifischer IgA-Antikörper. Die bei den Serotypen beobachtbare Kreuzreaktivität spiegelt sich nicht in Kreuzimmunität wider.


BALEAP News April 2020


Convalescent Plasma, an Apheresis Research Project Targeting and Motivating the Fully Recovered COVID 19 Patients: A Rousing Message of Clinical Benefit To Both Donors and Recipients Alike


docid: cbiwnszh

title: Assisted Living and Infection Prevention and Control


The exacerbation of burnout during COVID19: A major concern for nurse safety


A propósito del nuevo coronavirus: Microbioturismo


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