title: Ethics, Pandemic Planning and Communications

text: In this article we examine the role and ethics of communications in planning for an influenza pandemic. We argue that ethical communication must not only he effective, so that pandemic plans can be successfully implemented, communications should also take specific account of the needs of the disadvantaged, so that they are not further disenfranchised. This will require particular attention to the role of the mainstream media which may disadvantage the vulnerable through misrepresentation and exclusion.


title: TRIPS-plus and access to medicines in China

text: Ample evidence shows that Trade-related aspects of intellectual property rights (TRIPS)-plus provisions have seriously affected access to and availability of drugs in the developing countries. In recent years, developed countries have pressured many developing countries to implement TRIPS with stronger intellectual property (IP) protection than required by the TRIPS Agreement. The stronger provisions are called TRIPS-Plus provisions. This article focuses on IP and the health implications of limited access to medicines in China, explores the TRIPS-plus arrangements in Chinese IP laws and regulations, and makes suggestions for China's negotiation strategy in resisting pressure from developed countries to tighten IP laws and regulations.


title: A multi-regions discrete-time epidemic model with a travel-blocking vicinity optimal control approach on patches

text: We study, in this paper, infection dynamics when an epidemic emerges to many regions which are connected with their neighbors by any kind of anthropological movement. For this, we devise a multi-regions discrete-time model with the three classical SIR compartments, describing the spatial-temporal behaviors of homogenous susceptible, infected and removed populations. We suppose a large geographical domain, presented by a grid of colored cells, to exhibit at each instant i the spatial propagation of an epidemic which affects its different parts or sub-domains that we call here cells or regions. In order to minimize the number of infected individuals in some regions, we suggest an optimal control approach based on a travel-blocking vicinity strategy which aims to control a group of cells, or a patch, by restricting movements of infected people coming from its neighboring cells. We apply a discrete version of Pontryagin’s maximum principle to state the necessary conditions and characterization of the travel-blocking optimal controls. We provide cellular simulations based on discrete progressive-regressive iterative schemes associated with the obtained multi-points boundary value problems. For illustrating the modeling and optimal control approaches, we consider an example of 100 regions.


Inhaltsverzeichnis


Abstracts from USCAP 2019: Infectious Disease Pathology (1435-1462)


title: Public Health Research Priorities For The Future

text: The last century of innovative public health discoveries has led most of the world’s population to lead longer, healthier lives. Yet, the future holds some of the greatest public health challenges in mankind’s history. Global disparities in health; medication safety; climate change; epidemics of obesity and diabetes; an aging world demographic; and emerging infections all represent problems requiring scientific solutions. The solutions to these problems, like the solutions to those in the last century that contributed so greatly to our quality of life, will require paradigm-shifting innovation. To maximize individual innovative potential, one strategy is formal instruction in the methods of innovative thinking. Teaching innovative thinking is rarely integrated into science training. However 40 years of accumulated evidence suggests that formal instruction results in improved thinking skills. I describe here some of the methods integrated into a course for graduate and professional health science students entitled Innovative Thinking. The curriculum consists of three components: recognizing and finding alternatives to habitual cognitive patterns; learning to use tools that enhance idea generation and originality; and harmonizing divergent thinking with the process of convergent thinking that is central to the scientific method. To build more innovative environments, institutions can promote team science, fund staged scientific designs that are heavy on early prototypes, reward and grow the training programs of past innovators, and become less risk averse. Although public health has accomplished much, it must continue to battle major, growing causes of disease and disability. Innovation is the engine of scientific discovery. Releasing the great potential for discovery in all of us must be central to forwarding health and prosperity in the world.


Drug-resistant Plasmodium falciparum: are recent advances a cause for optimism?


title: Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents

text: AIM: The recurring resistance of the malaria parasite to many drugs compels the design of innovative chemical entities in antimalarial research. Pan-histone deacetylase inhibitors (pan-HDACis) have recently been presented in the literature as powerful novel antimalarials, although their application is hampered due to toxic side effects. This drawback might be neutralized by the deployment of isoform-selective HDACis. RESULTS: In this study, 42 thiaheterocyclic benzohydroxamic acids, 17 of them being potent and selective hHDAC6 inhibitors, were tested to investigate a possible correlation between hHDAC6 inhibition and antiplasmodial activity. CONCLUSION: Four hHDAC6 inhibitors showed submicromolar potency against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with high selectivity indices, pointing to the relevance of exploring hHDAC6 inhibitors as potential new antiplasmodial agents.


title: Dual-functioning antimalarials that inhibit the chloroquine-resistance transporter

text: Malaria remains a major international health challenge. Resistance to a number of existing drugs and evidence of the emergence of artemisinin resistance has emphasized the need for new antimalarials. A new approach has been the preparation of dual-function compounds that include a chloroquine-like antimalarial group and a group that resembles a chloroquine chemosensitizer. This article reviews the recent discovery of such dual-function antimalarials that are proposed to target both hemozoin formation and the chloroquine resistance transporter, PfCRT. These are discussed in relation to the mechanism of action of 4-aminoquinolines, chloroquine resistance and resistance reversal.


title: Design, synthesis, heme binding and density functional theory studies of isoindoline-dione-4-aminoquinolines as potential antiplasmodials

text: AIM: WHO Malaria report 2017 estimated 216 million cases of malaria and 445,000 deaths worldwide, with 91% of deaths affecting the African region. RESULTS/METHODOLOGY: Microwave promoted the synthesis of cycloalkyl amine substituted isoindoline-1,3-dione-4-aminoquinolines was urbanized for evaluating their antiplasmodial activities. Compound with the optimum combination of propyl chain length and hydroxyethyl piperazine proved to be the most potent among the synthesized scaffolds against chloroquine-resistant W2 strain of Plasmodium falciparum with an IC(50) value of 0.006 μM. Heme-binding along with density functional theory studies were further carried out in order to delineate the mechanism of action of the most active compound. CONCLUSION: The synthesized scaffold can act as a therapeutic template for further synthetic modifications toward the search for a new antimalarial agent.


title: Assay for screening for six antimalarial drugs and one metabolite using dried blood spot sampling, sequential extraction and ion-trap detection

text: BACKGROUND: More parasites are becoming resistant to antimalarial drugs, and in many areas a change in first-line drug treatment is necessary. The aim of the developed assay is to help determine drug use in these areas and also to be a complement to interviewing patients, which will increase reliability of surveys. RESULTS: This assay detects quinine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, chloroquine and its metabolite desethylchloroquine in a 100-µl dried blood spot. Most of the drugs also have long half-lives that make them detectable at least 7 days after administration. The drugs are extracted from the dried blood spot with sequential extraction (due to the big differences in physicochemical properties), solid-phase extraction is used as sample clean-up and separation is performed with gradient-LC with MS ion-trap detection. CONCLUSION: Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for all drugs except lumefantrine (200 ng/ml), and thus can be used to determine patient compliance. A major advantage of using the ion-trap MS it that it will be possible to go back into the data and look for other drugs as needed.


title: Development and validation of an HILIC–MS/MS method by one-step precipitation for chloroquine in miniature pig plasma

text: BACKGROUND: Quantification of polar compounds such as chloroquine by revered-phase LC is a challenge because of poor retention and silanol interactions with stationary phase. Strong ion-pairing reagents added to mobile phases to improve reversed-phase retention and improve peak shape can be harmful for MS. RESULTS: This new approach provides a rapid and sensitive method for the detection of chloroquine using hydrophilic interaction LC coupled to MS/MS (HILIC–MS/MS). Ammonium formate and formic acid were added to mobile phase to attain good peak shapes and the salified chloroquine as well retained in an HILIC column. Linearity, intra- and inter-day precision, accuracy, recovery, matrix effect and stability were evaluated during the validation process. CONCLUSION: The validated method has been successfully used in a PK study in miniature pigs, and paves way for future development.


title: SLCO1A2, SLCO1B1 and SLCO2B1 polymorphisms influences chloroquine and primaquine treatment in Plasmodium vivax malaria

text: AIM: The association of transporters gene polymorphisms with chloroquine/primaquine malaria treatment response was investigated in a Brazilian population. PATIENTS & METHODS: Totally, 164 Plasmodium vivax malaria infected patients were included. Generalized estimating equations were performed to determine gene influences on parasitemia and/or gametocytemia clearance over treatment time. RESULTS: Significant interaction between SLCO2B1 genotypes and treatment over time for parasitemia clearance rate on day 2 were observed (p (FDR) = 0.002). SLCO1A2 and SLCO1B1 gene treatment over time interactions were associated with gametocytemia clearance rate (p (FDR) = 0.018 and p (FDR) = 0.024). ABCB1, ABCC4 and SLCO1B3 were not associated with treatment response. CONCLUSION: The present work presents the first pharmacogenetic report of an association between chloroquine/primaquine responses with OATP transporters.


title: The effect of SNPs in CYP450 in chloroquine/primaquine Plasmodium vivax malaria treatment

text: BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients. RESULTS: An effect of CYP2C8 low-activity alleles on treatment was observed (p = 0.01). From baseline to first day of treatment, wild-type individuals achieved greater reduction of gametocytes than low-activity allele carriers. CYP2C9 and CYP3A5 genes showed a trend for gametocytemia and parasitemia clearance rates. CONCLUSION: Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment.


title: Non-invasive lung disease diagnostics from exhaled microdroplets of lung fluid: perspectives and technical challenges

text: The combination of ultra-sensitive assay techniques and recent improvements in the instrumentation used to collect microdroplets of lung fluid (MLF) from exhaled breath has enabled the development of non-invasive lung disease diagnostics that are based on MLF analysis. In one example of this approach, electrospun nylon filters were used to collect MLFs from patients with pulmonary tuberculosis. The filters were washed to obtain liquid probes, which were then tested for human immunoglobulin A (h-IgA) and fractions of h-IgA specific to ESAT-6 and Psts-1, two antigens secreted by Mycobacterium tuberculosis. Probes collected for 10 min contained 100–1500 fg of h-IgA and, in patients with pulmonary tuberculosis, a portion of these h-IgA molecules showed specificity to the secreted antigens. Separate MLFs and their dry residues were successfully collected using an electrostatic collector and impactor developed especially for this purpose. Visualization of MLF dry residues by atomic force microscopy made it possible to estimate the lipid content in each MLF and revealed mucin molecules in some MLFs. This exciting new approach will likely make it possible to detect biomarkers in individual MLFs. MLFs emerging from an infection site (‘hot’ microdroplets) are expected to be enriched with infection biomarkers. This paper discusses possible experimental approaches to detecting biomarkers in single MLFs, as well as certain technological problems that need to be resolved in order to develop new non-invasive diagnostics based on analysing biomarkers in separate MLFs.


Commentary: Global Preparedness for Public Health Emergencies


title: Simulations for epidemiology and public health education

text: Recent and potential outbreaks of infectious diseases are triggering interest in predicting epidemic dynamics on a national scale and testing the efficacies of different combinations of public health policies. Network-based simulations are proving their worth as tools for addressing epidemiology and public health issues considered too complex for field investigations and questionnaire analyses. Universities and research centres are therefore using network-based simulations as teaching tools for epidemiology and public health education students, but instructors are discovering that constructing appropriate network models and epidemic simulations are difficult tasks in terms of individual movement and contact patterns. In this paper we will describe (a) a four-category framework (based on demographic and geographic properties) to discuss ways of applying network-based simulation approaches to undergraduate students and novice researchers; (b) our experiences simulating the transmission dynamics of two infectious disease scenarios in Taiwan (HIV and influenza); (c) evaluation results indicating significant improvement in student knowledge of epidemic transmission dynamics and the efficacies of various public health policy suites; and (d) a geospatial modelling approach that integrates a national commuting network as well as multi-scale contact structures.


9th Congress of Infectious Diseases and Tropical Medicine: This issue is available online at www.springerlink.com/content/1439-0973


title: Healing Health Care: From Sick Care Towards Salutogenic Healing Systems

text: Aaron Antonovsky’s salutogenic model is starting to impact health promotion at the level of theory and research. However, the benefits of Antonovsky’s theory for population health promotion practices and health care restructuring are unrealized. This analysis uses the definition of health derived from complexity science as a lifelong, multidimensional adaptive process comprised of intersecting biological, psychological, social, environmental, and spiritual systems as a starting point for a salutogenic analysis of formal healthcare. Following Antonovsky’s criticism of contemporary healthcare as resting upon a pathogenic paradigm, I outline four general shortcomings associated with the pathogenic approach to healthcare. The basic elements of a healthcare system designed according to principles derived from Antonovsky’s salutogenic model of health are then presented. It is argued that Antonovsky’s theory offers a productive basis for conceptualizing health and healthcare systems in that it allows us to grasp that debates between population health promotion and providing medical care, are, at their root, unproductive debates predicated on a false dichotomy. A salutogenic healthcare system is one which pays credence to the nested complexity of human health and strives to strike an adaptive balance between health production and the provision of medical care.


title: Global dynamics for discrete-time analog of viral infection model with nonlinear incidence and CTL immune response

text: In this paper, a discrete-time analog of a viral infection model with nonlinear incidence and CTL immune response is established by using the Micken non-standard finite difference scheme. The two basic reproduction numbers [Formula: see text] and [Formula: see text] are defined. The basic properties on the positivity and boundedness of solutions and the existence of the virus-free, the no-immune, and the infected equilibria are established. By using the Lyapunov functions and linearization methods, the global stability of the equilibria for the model is established. That is, when [Formula: see text] then the virus-free equilibrium is globally asymptotically stable, and under the additional assumption [Formula: see text] when [Formula: see text] and [Formula: see text] then the no-immune equilibrium is globally asymptotically stable and when [Formula: see text] and [Formula: see text] then the infected equilibrium is globally asymptotically stable. Furthermore, the numerical simulations show that even if assumption [Formula: see text] does not hold, the no-immune equilibrium and the infected equilibrium also may be globally asymptotically stable.


title: The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

text: BACKGROUND: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS: We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS: Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high–level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS: DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.


title: Pseudomonas infections among hospitalized adults in Latin America: a systematic review and meta-analysis

text: BACKGROUND: Treatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM. METHODS: MEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar. RESULTS: The screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28–0.81; I(2) = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28–0.81; I(2) = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates. CONCLUSION: Our study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.


title: Rare cause of repeated pulmonary embolism: a case of primary pleural squamous cell carcinoma and literature review

text: BACKGROUND: Malignant tumors are risk factors for a pulmonary embolism (PE), and a PE caused by a tumor is not uncommon. Primary pleural squamous cell carcinoma (PPSCC) is a rare malignancy; thus, a related PE is extremely rare. CASE PRESENTATION: A previously healthy 49-year-old female patient was admitted to Northern Jiangsu People’s Hospital owing to chest tightness, cough, and breathing difficulty that persisted for 3 days. Following admission, a computed tomography (CT) pulmonary angiography revealed an embolism in the main pulmonary artery, upper and lower pulmonary artery branch. The patient was treated with alteplase, warfarin, and antibiotics. Over the following year, she experienced recurrent chest pain and tightness and breathing difficulty, with multiple CT pulmonary angiography revealing thrombosis in the right and left main pulmonary artery. No abnormalities were observed in surrogate markers of autoimmune diseases, tumor antigen testing, or ultrasonography; thus, the cause of recurrent PE was not identified. Subsequently, a positron emission tomography-computed tomography (PET-CT) examination revealed diffuse heterogeneous thickening of the right pleura and substantially increased glucose metabolism. A CT-guided pleural biopsy was performed, and histopathological examination of the pleura eventually revealed a diagnosis of PPSCC. CONCLUSIONS: PPSCC is a rare tumor that lacks specific clinical manifestations and is difficult to detect with imaging techniques. The occurrence of PE as the primary manifesting symptom in a patient with PPSCC is extremely rare. Thus, malignant tumors should be considered in patients with no risk factors for PE and/or in those with recurrent PE. An immediate diagnosis and adequate intervention can be achieved with increased awareness of this diagnosis and subsequent related examinations.


title: Bioattack or Panic Attack? Critical Reflections on the Ill-logic of Bioterrorism and Biowarfare in Late/Postmodernity

text: This paper casts a critical sociological eye over the pros and cons of bioterrorism and biowarfare in the wake of September 11(th). The first part of the paper provides a brief sketch of the (not so) secret history of chemical and biological weapons (CBW), including arguments for and against their military/terrorist deployment to date. The sociological themes and issues this raises are then more fully explored in the remainder of the paper, with particular reference to: (i) (epidemics of) fear/panic; (ii) risk/(mis)trust; (iii) security/surveillance; (iv) combat/code. The paper concludes with some further thoughts and reflections on these global matters, and the relays between social theory and health they signal, including both the ‘war on terrorism’ and the health implications of war in general.


Neue Ansätze im Kampf gegen Problemkeime: Infektiologie


title: A simulation model for policy decision analysis: a case of pandemic influenza on a university campus

text: Pandemic influenza preparedness plans strongly focus on efficient mitigation strategies including social distancing, logistics and medical response. These strategies are formed by multiple decision makers before a pandemic outbreak and during the pandemic in local communities, states and nation-wide. In this paper, we model the spread of pandemic influenza in a local community, a university, and evaluate the mitigation policies. Since the development of an appropriate vaccine requires a significant amount of time and available antiviral quantities can only cover a relatively small proportion of the population, university decision makers will first focus on non-pharmaceutical interventions. These interventions include social distancing and isolation. The disease spread is modelled as differential equations-based compartmental model. The system is simulated for multiple non-pharmaceutical interventions such as social distancing including suspending university operations, evacuating dorms and isolation of infected individuals on campus. Although the model is built based on the preparedness plan of one of the biggest universities in the world, Arizona State University, it can easily be generalized for other colleges and universities. The policies and the decisions are tested by several simulation runs and evaluations of the mitigation strategies are presented in the paper.


title: Politics of International Health in the Bush Administration

text: Henry A. Waxman reviews the politicization of international health by the Bush Administration in three areas: tobacco control, nutrition, and reproductive health. He discusses how politics may threaten the President's primary international health commitment on HIV/AIDS. Taken as a whole, these and other actions have frequently left the United States isolated in its positions and have undermined public health progress across the globe.


title: Anti-Viral Activity of Indian Plants

text: Plants continue to be a major source for new chemical entities to develop novel therapeutic agents. Large number of plants has been shown to be active in vitro against a variety of human pathogenic viruses or their near congeners. In several cases the active compounds have been isolated and characterized. Very few of them, however, have been investigated in detail in vivo or taken to the clinic. Pure compounds like andrographolide, curcumin and glycyrrhizic acid as well as extracts of Azadirachta indica have shown activity against several viruses and should be investigated further for their therapeutic potential. An analysis of available data from several hundred species indicates that antiviral activity is more likely to be found in plants belonging to certain families. It is necessary to screen more plants of these families which are available in India to obtain further leads.


title: Applications of simulation within the healthcare context

text: A large number of studies have applied simulation to a multitude of issues relating to healthcare. These studies have been published in a number of unrelated publishing outlets, which may hamper the widespread reference and use of such resources. In this paper, we analyse existing research in healthcare simulation in order to categorise and synthesise it in a meaningful manner. Hence, the aim of this paper is to conduct a review of the literature pertaining to simulation research within healthcare in order to ascertain its current development. A review of approximately 250 high-quality journal papers published between 1970 and 2007 on healthcare-related simulation research was conducted. The results present a classification of the healthcare publications according to the simulation techniques they employ; the impact of published literature in healthcare simulation; a report on demonstration and implementation of the studies’ results; the sources of funding; and the software used. Healthcare planners and researchers will benefit from this study by having ready access to an indicative article collection of simulation techniques applied to healthcare problems that are clustered under meaningful headings. This study facilitates the understanding of the potential of different simulation techniques in solving diverse healthcare problems.


title: Mapping of Medical Microbiology Content in a Clinical Presentation Curriculum

text: Clinically important microbes, and the pathogenesis, symptoms and diagnosis of their corresponding infectious diseases were integrated into clinical schemes within a clinical presentation curriculum. Decisions on microbe placement considered a variety of factors, including spaced reinforcement of major pathogens. We report here the map of our integrated medical microbiology curriculum.


title: Global stability of the endemic equilibrium of a discrete SIR epidemic model

text: The basic reproductive number [Formula: see text] of a discrete SIR epidemic model is defined and the dynamical behavior of the model is studied. It is proved that the disease free equilibrium is globally asymptotically stable if [Formula: see text], and the persistence of the model is obtained when [Formula: see text]. The main attention is paid to the global stability of the endemic equilibrium. Sufficient conditions for the global stability of the endemic equilibrium are established by using the comparison principle. Numerical simulations are done to show our theoretical results and to demonstrate the complicated dynamics of the model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1687-1847-2013-42) contains supplementary material, which is available to authorized users.


Influenza Moves to the Front of Public Health Concerns


title: Global health diplomacy for obesity prevention: Lessons from tobacco control

text: To date the global health diplomacy agenda has focused primarily on infectious diseases. Policymakers have not dedicated the same level of attention to chronic diseases, despite their rising contribution to the global burden of disease. Negotiation of the Framework convention on tobacco control provides an apt example from global health diplomacy to tackle diet-related chronic diseases. What lessons can be learned from this experience for preventing obesity? This article looks at why a global policy response is necessary, at the actors and interests involved in the negotiations, and at the forum for diplomacy.


title: Molecular and Nanotechnologic Approaches to Etiologic Diagnosis of Infectious Syndromes

text: Infectious diseases are a major global public health problem. Multiple agents are now recognized to cause indistinguishable illnesses. The term ‘syndrome’ applies to such situations, for which early and rapid diagnosis of the infecting agent would enable prompt and appropriate therapy. Public health physicians would also get timely information on the specific etiology of the infectious syndrome, facilitating intervention at the community level in the face of outbreaks or epidemics. A variety of molecular techniques have been evaluated for rapid diagnosis of infectious syndromes. These techniques include real-time multiplex PCR, DNA microarray, loop-mediated isothermal amplification, and other similar assays. This review surveys such state-of-the-art technologies.


title: Evidence vs experience in neonatal practices in necrotizing enterocolitis

text: INTRODUCTION: Necrotizing enterocolitis (NEC) has been recognized for over 40 years as a cause of inflammation and necrosis of the small and large intestine of infants born at less than 36 weeks of gestation. NEC remains a significant health problem for infants born prematurely and may become the leading cause of morbidity and mortality among these infants worldwide. The sequence of events leading to NEC is complex and multifactorial, although damage to the intestinal epithelium and invasion by bacteria are known to play central roles in disease pathogenesis. STUDY DESIGN: Bacteria initiate a cascade of inflammation that may progress to intestinal necrosis and perforation with sepsis and death. RESULT: Treatment of infants at risk for NEC with probiotic bacteria may be an area of great potential, as probiotic bacteria may promote maturation of the epithelial barrier and function to exclude bacterial pathogens from critical niches in the intestine, thereby disrupting a primary pathway in disease pathogenesis. CONCLUSION: Understanding how probiotic bacteria, or other novel therapies, prevent or limit disease propagation in NEC will be paramount in limiting the impact of disease in a growing population of premature newborns.


title: How resilient is the United States’ food system to pandemics?

text: Rarely have studies focused on the second- and third-order effects of pandemics. Limiting the disruption of critical infrastructures during a pandemic is important for the survival and health of society (i.e., electricity, water, and food) as most medical and public health responses to a pandemic depend on these infrastructures. The studies that have looked at this issue have highlighted alarming gaps in preparedness. This study used a system dynamics model to demonstrate the likely effects of a pandemic on the USA’s food system. The model reveals that a severe pandemic with greater than a 25 % reduction in labor availability can create significant and widespread food shortages. The Ebola epidemic that began in 2014 has caused severe food shortages in West Africa, which are similar to the effects that this model predicts in the USA. The likely effects of the reduction in the amount of available food are difficult to specifically predict; however, it is likely to have severe negative consequences on society. The resilience of the food system must be improved against this hazard and others. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13412-015-0275-3) contains supplementary material, which is available to authorized users.


title: Excess mortality from seasonal influenza is negligible below the age of 50 in Israel: implications for vaccine policy

text: PURPOSE: Evaluation of the severity of pandemic influenza requires reliable estimates of mortality attributable to the seasonal influenza. METHODS: Excess age-specific mortality during periods of influenza activity was evaluated in Israel during the period 1999–2006 for three death categories. For each respiratory year, the lowest monthly moving average for the mortality rate was subtracted from each month in the period of influenza activity. Average mortality rates in years with minimal influenza activity were deducted from corresponding months to exclude winter mortality unrelated to influenza. The sums of these results were used as estimates of excess mortality rates. RESULTS: Overall excess mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4 to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was associated with an average of 869 (range 280–1,516) deaths annually from respiratory and circulatory diseases during seasons with significant influenza activity. About 90% of the influenza-associated mortality from respiratory and circulatory diseases was in the age group 65+ years and about 1% in the age group <50 years. The age group <50 years accounted for an annual average of seven deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality associated with seasonal influenza is highly variable. Under the age of 50 years, there is minimal seasonal influenza associated mortality. This information provides an important baseline for evaluating the severity of the A(H1N1) 2009 influenza pandemic, where persons under 50 years of age were often disproportionately represented.


title: ExoU-induced redox imbalance and oxidative stress in airway epithelial cells during Pseudomonas aeruginosa pneumosepsis

text: ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of severe lung infection and sepsis. Because inflammation is usually associated with oxidative stress, we investigated the effect of ExoU on free radical production and antioxidant defense mechanisms during the course of P. aeruginosa infection. In an experimental model of acute pneumonia, ExoU accounted for increased lipid peroxidation in mice lungs as soon as 3 h after intratracheal instillation of PA103 P. aeruginosa strain. The contribution of airway cells to the generation of a redox imbalance was assessed by in vitro tests carried out with A549 airway epithelial cells. Cultures infected with the ExoU-producing PA103 P. aeruginosa strain produced significantly increased concentrations of lipid hydroperoxides, 8-isoprostane, reactive oxygen intermediates, peroxynitrite and nitric oxide (NO), when compared to cells infected with exoU-deficient mutants. Overproduction of NO by PA103-infected cells likely resulted from overexpression of both inducible and endothelial NO synthase isoforms. PA103 infection was also associated with a significantly increased activity of superoxide dismutase (SOD) and decreased levels of reduced glutathione (GSH), a major antioxidant compound. Our findings unveil another potential mechanism of tissue damage during infection by ExoU-producing P. aeruginosa strains.


title: Relationship between circulating levels of angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis and coronary heart disease

text: As a counter-regulatory arm of the renin angiotensin system (RAS), the angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis (ACE2-Ang-(1–7)-MAS axis) plays a protective role in cardiovascular diseases. However, the link between circulating levels of ACE2-Ang-(1–7)-Mas axis and coronary atherosclerosis in humans is not determined. The object of present study was to investigate the association of circulating levels of ACE2, Ang-(1–7) and Ang-(1–9) with coronary heart disease (CHD) defined by coronary angiography (CAG). 275 patients who were referred to CAG for the evaluation of suspected CHD were enrolled and divided into two groups: CHD group (diameter narrowing ≥ 50%, n = 218) and non-CHD group (diameter narrowing < 50%, n = 57). Circulating ACE2, Ang-(1–7) and Ang-(1–9) levels were detected by enzyme-linked immunosorbent assay (ELISA). In females, circulating ACE2 levels were higher in the CHD group than in the non-CHD group (5617.16 ± 5206.67 vs. 3124.06 ± 3005.36 pg/ml, P = 0.009), and subgroup analysis showed the significant differences in ACE2 levels between the two groups only exist in patients with multi-vessel lesions (P = 0.009). In multivariate logistic regression, compared with the people in the lowest ACE2 quartile, those in the highest quartile had an OR of 4.33 (95% CI 1.20–15.61) for the CHD (P for trend = 0.025), the OR was 5.94 (95% CI 1.08–32.51) for the third ACE2 quartile and 9.58 (95% CI 1.61–56.95) for the highest ACE2 quartile after adjusting for potential confounders (P for trend = 0.022). However, circulating Ang-(1–7) and Ang-(1–9) levels had no significant differences between the two groups. In males, there were no significant differences in the levels of ACE2-Ang-(1–7)-MAS axis between two groups. Together, circulating ACE2 levels, but not Ang-(1–7) and Ang-(1–9) levels, significantly increased in female CHD group when compared with non-CHD group, increased ACE2 was independently associated with CHD in female and in patients with multi-vessel lesions even after adjusting for the confounding factors, indicating that ACE2 may participate as a compensatory mechanism in CHD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00380-019-01478-y) contains supplementary material, which is available to authorized users.


title: Systemische Hantavirus-Infektion bei einem komatösen HIV Patienten

text: SYMPTOMS: A 40 year old, disoriented, HIV- and Hepatitis B positive male patient was admitted with 40.3 °C. Clinically he presented a sinustachycardia (160/min) and hypotension (70/60 mmHg). INVESTIGATIONS/DIAGNOSIS: Laboratory analyses showed elevated infection parameters, azotemia, proteinuria and thrombopenia. CD(4+)T-helper cells: 320/µl (32 %), HIV RNA: < 40 copies/ml, Hepatitis B DNA: 20800 copies/ml. Hantavirus serology (immunofluorescence antibody assay): 1:2048; serotype Puumala. TREATMENT/COURSE: An early-goal-directed therapy and antibiotic treatment with Piperacillin and Tazobactam was initiated. The patient developed a bipulmonal infiltrate and an acute respiratory distress syndrome (ARDS ) requiring tracheal intubation, as well as a triad of fever, renal failure and profound hemorrhagic symptoms. This led to the diagnosis of the Puumala infection. Due to the parallel HIV- and Hepatits B infection an antiretroviral therapy was initiated. CONCLUSION: In summary the Puumala infection bears the potential for a severe multi-organ failure, which is not typical for this usually benign infection.


title: Modulation of Sodium Transport in Alveolar Epithelial Cells by Estradiol and Progesterone

text: The effects of estradiol (E2) and progesterone (P) on alveolar epithelial Na(+) transport were studied in isolated alveolar epithelial cells from 18- to 19-d GA rat fetuses, grown to confluence in serum-free media supplemented with E2 (0–1 μM) and P (0–2.8 μM). Short-circuit currents (I(SC)) were measured, showing an increase by E2 and P in a dose-dependent manner. The Na,K-ATPase subunits -α(1) and -β(1) were detected by Western blotting, but total expression was not significantly altered. Furthermore, all three epithelial Na(+) channel (ENaC) subunits -α, -β, and -γ were detected, with trends toward a higher expression in the presence of E2 and P. Real-time PCR revealed an increase of α- and β-ENaC expression but no alteration of γ-ENaC. In addition, the mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) and Na,K-ATPase-β(1) subunit were elevated in the presence of E2 and P. Single-channel patch clamp analysis demonstrated putative highly selective and nonselective cation channels in the analyzed cells, with a higher percentage of responsive patches under the influence of E2 and P. We conclude that E2 and P increased Na(+) transport in alveolar epithelial cells by enhancing the expression and activity of ENaC and Na,K-ATPase.


title: H1N1 Encephalitis with Malignant Edema and Review of Neurologic Complications from Influenza

text: BACKGROUND: Influenza virus infection of the respiratory tract is associated with a range of neurologic complications. The emergence of 2009 pandemic influenza A (H1N1) virus has been linked to neurological complications, including encephalopathy and encephalitis. METHODS: Case report and literature review. RESULTS: We reviewed case management of a 20-year old Hispanic male who developed febrile upper respiratory tract signs and symptoms followed by a confusional state. He had rapid neurologic decline and his clinical course was complicated by refractory seizures and malignant brain edema. He was managed with oseltamavir and peramavir, corticosteroids, intravenous gamma globulin treatment, anticonvulsants, intracranial pressure management with external ventricular drain placement, hyperosmolar therapy, sedation, and mechanical ventilation. Reverse transcriptase polymerase chain reaction analysis of nasal secretions confirmed 2009 H1N1 virus infection; cerebrospinal fluid (CSF) was negative for 2009 H1N1 viral RNA. Follow-up imaging demonstrated improvement in brain edema but restricted diffusion in the basal ganglia. We provide a review of the clinical spectrum of neurologic complications of seasonal influenza and 2009 H1N1, and current approaches towards managing these complications. CONCLUSIONS: 2009 H1N1-associated acute encephalitis and encephalopathy appear to be variable in severity, including a subset of patients with a malignant clinical course complicated by high morbidity and mortality. Since the H1N1 influenza virus has not been detected in the CSF or brain tissue in patients with this diagnosis, the emerging view is that the host immune response plays a key role in pathogenesis.


Genomics and a Scientifically Responsible Ethics


title: IFITM3 and severe influenza virus infection. No evidence of genetic association

text: Influenza virus infection (IVI) is typically subclinical or causes a self-limiting upper respiratory disease. However, in a small subset of patients IVI rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a minority of patients require intensive care unit admission. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IVI. However, the molecular basis of such human factors remains largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is associated with a population-attributable risk of 5.4 % for severe IVI in Northern Europeans and 54.3 % for severe H1N1pdm infection in Chinese. A total of 148 patients with confirmed IVI were considered for recruitment; 118 Spanish patients (60 of them hospitalized with PVP) and 246 healthy Spanish individuals were finally included in the statistical analysis. PCR-RFLP was used with confirmation by Sanger sequencing. The allele frequency for rs12252-C was found to be 3.5 % among the general Spanish population. We found no rs12252-C homozygous individuals in our control group. The only Spanish patient homozygous for rs12252-C had a neurological disorder (a known risk factor for severe IVI) and mild influenza. Our data do not suggest a role of rs12252-C in the development of severe IVI in our population. These data may be relevant to recognize whether patients homozygous for rs12252-C are at risk of severe influenza, and hence require individualized measures in the case of IVI.


Abstracts der 43. gemeinsamen Jahrestagung der DGIIN und ÖGIAIM


title: Embracing microbes in exposure science

text: Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.


title: Nosocomial Pneumonia: Rationalizing the Approach to Empirical Therapy

text: Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2–3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus (‘core pathogens’). Empirical therapy covering only the ‘core pathogens’ will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (≥5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus- baumannii, Stenotrophomonas maltophilia and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance. Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.


Neurocritical Care Society 8(th) Annual Meeting


title: Autologous hematopoietic stem cell transplantation for high-risk brain tumors in children

text: Autologous hematopoietic stem cell transplant (AHSCT) has been advocated as a form of salvage therapy for children with high-risk or relapsed brain tumors but only limited data are available currently. We report the outcomes of pediatric brain tumors treated with AHSCT in a quaternary referral center in Hong Kong over 10 years (June 1996–May 2006). Thirteen patients with medulloblastoma (n = 9), cerebral primitive neuroectodermal tumor (n = 1), ependymoma (n = 1), germ cell tumor (n = 1) and cerebellar rhabdoid (n = 1) were transplanted because of tumor residual (n = 1) or recurrence (n = 12). Uniform upfront treatment protocols were adopted according to specific tumor types. Prior to AHSCT, 8 patients (61.5%) achieved complete remission and 5 (38.5%) were in partial remission. Conditioning employed thiotepa 300 mg/m(2), etoposide 250 mg/m(2 )and carboplatin 500 mg/m(2) daily for 3 days. Toxicity included mucositis and neutropenic fever in all patients, grade 4 hepatic toxicity in 4 patients (including hepatic veno-occlusive disease in 2 patients) and grade 4 renal toxicity in 1 patient. The 5-year event-free survival was 53.9%. Five patients died of disease recurrence or progression 8–21 months after transplant with a median disease-free period of 8 months post-transplant. One died of transplant-related complications in the early post-transplant period. Seven survived for a median of 5.4 years (maximum follow-up of 9.8 years), with six having Lansky-Karnofsky performance score above 80. All survivors had complete remission before transplant though 2 had leptomeningeal spread. We conclude that AHSCT can achieve long-term survival in children with recurrent brain tumor. However, those with macroscopic residual tumor before transplant cannot be salvaged.


Neurocritical Care Society 11th Annual Meeting: October 1-4, 2013 Philadelphia Marriott Downtown Hotel Philadelphia, Pennsylvania


title: Extracorporeal membrane oxygenation for blastomycosis-related acute respiratory distress syndrome: a case series

text: PURPOSE: Blastomyces dermatitidis is a dimorphic fungus endemic to North America capable of causing fatal respiratory failure. Acute respiratory distress syndrome (ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients and carries a mortality of 50-90%. This report describes the clinical course of four consecutive patients with blastomycosis-related ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO) during 2009-2014. CLINICAL FEATURES: Four adults were referred from northwestern Ontario, Canada with progressive respiratory illnesses. All patients developed diffuse bilateral opacities on chest radiography and required mechanical ventilation within 6-72 hr. Patients satisfied Berlin criteria for severe ARDS with trough P(a)O(2)/F(i)O(2) ratios of 44-61 on positive end-expiratory pressure of 12-24 cm H(2)O. Wet mount microscopy from respiratory samples showed broad-based yeast consistent with B.dermatitidis. Despite lung protective ventilation strategies with maximal F(i)O(2) (patients A-D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and D), and prone positioning (patient D), progressive hypoxemia resulted in initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with subsequent de-escalation of ventilatory support. In all four cases, ECMO decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18-52 days), and the patients survived to hospital discharge (31-87 days). CONCLUSION: This report describes the successful application of ECMO as rescue therapy in aid of four patients with refractory blastomycosis-associated ARDS. In addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ECMO should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure.


17th Annual Meeting, Neurocritical Care Society, October 15–18, 2019, Vancouver, Canada


title: Activation of the Granzyme Pathway in Children With Severe Respiratory Syncytial Virus Infection

text: Granzymes (Grs), serine proteases present in granules of effector lymphocytes, are involved in several host immune responses, including the activation of cell death and inflammatory pathways. The main goal of this study was to determine whether the local cell-mediated Gr pathway is activated during severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in children. Tracheal aspirates (TA) from 23 children with RSV-LRTI and 12 controls without pulmonary disease were analyzed for Gr A and B. Bronchoalveolar lavage fluid samples from seven children with RSV-LRTI were analyzed for cellular expression of GrB. Levels of GrA and GrB in TA were significantly increased in RSV patients compared with controls and both Grs showed preserved activity. Gr levels correlated with the total leukocyte counts and IL-8 levels in the airways at several time points. However, no correlation between Gr levels and release of caspase-cleaved cytokeratin-18 was found. There was evidence for marked expression of GrB by both CD8(+) and CD4(+) T cells and natural killer cells in the respiratory tract. These findings suggest activation of the cell-mediated Gr pathway during severe RSV-LRTI in children.


title: Virtue ethics and public health: A practice-based analysis

text: Public health plays an important, albeit often unnoticed, role in protecting and promoting the health of populations. The activities of public health are complex, performed by multiple professionals, and range from the innocuous to the intrusive. Ethical analyses in public health reflect some of this complexity and fragmentation, with no one approach able to capture the full range of ethical considerations raised by public health activities. There are however, good reasons why we should pursue such analyses. Providing a robust ethical framework for public health may promote the identity and function of public health, address some of the shortcomings of utilitarianism, and help to combat the threat that public health faces through lack of political will in many parts of the world. In this paper I argue that Alasdair MacIntyre’s account of practices and virtues can make a valuable contribution to public health ethics. The first part of the paper argues that public health may properly be described as the type of practice that provides an arena for the exercise of virtues. This is followed by an analysis of the three virtues of honesty, courage and justice in public health practice. Using virtue theory captures morally important elements of public health and helps to maintain awareness of significant moral values in the practice of public health. Such awareness is crucial in maintaining and defending the integrity of public health.


title: Acute respiratory distress syndrome in a patient with primary myelofibrosis after ruxolitinib treatment discontinuation

text: Ruxolitinib is a Janus kinase (JAK) inhibitor used for the treatment of myelofibrosis with demonstrated efficacy for the alleviation of disease-related symptoms and splenomegaly. Anemia and thrombocytopenia are the main secondary effects. However, there are case reports of rare but serious adverse events following drug withdrawal. We present a case of a 76-year-old man diagnosed with primary myelofibrosis who presented with constitutional symptoms and symptomatic splenomegaly. Ruxolitinib was started (15 mg twice daily) and his disease-related symptoms disappeared. Six weeks later, he developed grade 4 thrombocytopenia and grade 3 anemia. Ruxolitinib was stopped and corticosteroid treatment (prednisone 1 mg/kg/day) was started to avoid a cytokine-rebound reaction. The patient then developed fever, chills, a biological inflammatory syndrome, and an acute respiratory disease syndrome. Full workup excluded an infection and we concluded that ruxolitinib withdrawal syndrome was the likely cause. Continued treatment with corticosteroids, as well as oxygen supply and continuous positive airway pressure, allowed an alleviation of his symptoms. This case report describes acute respiratory distress syndrome as another potential complication of ruxolitinib withdrawal syndrome.


title: Perioperative haemotherapy: II. Risks and complications of blood transfusion

text: Major life-threatening complications following blood transfusion are rare and human error remains an important aetiological factor in many. The infectious risk from blood transfusion is predominantly hepatitis, and non-A, non-B and hepatitis C (HCV) are the most common subtypes noted. The risk of posttransfusion hepatitis (PTH) appears to be decreasing and this is attributed to both deferral of high-risk donors and more aggressive screening of donated blood. Screening for HCV is expected to decrease this risk further. The risk of HIV transmission following blood transfusion is negligibly small. There are data to suggest that perioperative blood transfusion results in suppression of the recipient’s immune system. Earlier recurrence of cancer and an increased incidence of postoperative infection have been associated with perioperative blood transfusion although the evidence is not persuasive. Microaggregate blood filters are not recommended for routine blood transfusion but do have a role in the prophylaxis of non-haemolytic febrile reactions caused by platelet and granulocyte debris in the donor blood. Patients should be advised when there is likely to be a requirement for perioperative blood transfusion and informed consent for transfusion should be obtained.


title: Therapeutic Implications of Antibacterial Resistance in Community-Acquired Respiratory Tract Infections in Children

text: The global spread of antibacterial resistance has important implications for the current and future management of bacterial respiratory tract infections in children. Data suggest that emerging resistance to commonly prescribed antibacterials, such as macrolides and trimethoprim-sulfamethoxazole, is beginning to impact the treatment of these infections, which include acute otitis media, tonsillitis/pharyngitis and community-acquired pneumonia. There is, therefore, a need for additional agents that are active against common respiratory tract pathogens, including resistant strains and are suitable for use in children. Infection control measures to curb the clonal spread of antibacterial resistance are also extremely important.


title: Synthetic biology, security and governance

text: The twenty-first century has witnessed an increasing confluence of rapidly advancing science and its embodiment in practical technologies, an extensive global diffusion of the knowledge and capabilities associated with those developments, and a seemingly unending shift in the international security environment. The scope and intensity of these interactions in the life sciences have generated concern about security risks stemming from possible misuse. This lecture focuses on one of the key emerging life science technologies of concern, gene synthesis, and considers how the new risks and challenges it poses for governance can best be managed.


title: Meeting the Challenge of Epidemic Infectious Disease Outbreaks: An Agenda for Research

text: Challenges arising from epidemic infectious disease outbreaks can be more effectively met if traditional public health is enhanced by sociology. The focus is normally on biomedical aspects, the surveillance and sentinel systems for infectious diseases, and what needs to be done to bring outbreaks under control quickly. Social factors associated with infectious disease outbreaks are often neglected and the aftermath is ignored. These factors can affect outbreak severity, its rate and extent of spread, influencing the welfare of victims, their families, and their communities. We propose an agenda for research to meet the challenges of infectious disease outbreaks. What social factors led to the outbreak? What social factors affected its severity and rate and extent of spread? How did individuals, social groups, and the state react to it? What are the short- and long-term effects on individuals, social groups, and the larger society? What programs can be put in place to help victims, their families, and affected communities to cope with the consequences – impaired mental and physical health, economic losses, and disrupted communities? Although current research on infectious disease outbreaks pays attention to social factors related to causation, severity, rate and extent of spread, those dealing with the “social chaos” arising from outbreaks are usually neglected. Inclusion, by combining traditional public health with sociological analysis, will enrich public health theory and understanding of infectious disease outbreaks. Our approach will help develop better programs to combat outbreaks and equally important, to help survivors, their families, and their communities cope better with the aftermath.


title: Preparedness as a technology of (in)security: Pandemic influenza planning and the global biopolitics of emerging infectious disease

text: This article takes as its starting point the idea that re-emerging infectious disease has become a paradigmatic way of thinking about disease. The framing of infectious disease as a threat to global public health and economic security coincides with preemptive forms of control. A particular type of preemptive regulation is global pandemic influenza planning that entails the governing of an imminent, albeit uncertain, global health event. We examine the discourse of ‘preparedness’ within pandemic planning documents produced by the World Health Organization from 1999 to 2009. We present key findings on: the construction of the influenza virus in terms of its potential to transform and expand across corporeal and territorial boundaries; and the integration of pandemic preparedness into everyday practices. Our analysis illustrates how the discourse of preparedness links the justification for population-level preemptive approaches to discursive constructions of the virus. By articulating this relationship, this article contributes to understandings of the implications of ‘molecular’ constructions for the biopolitical regulation of the global population.


title: The Political Face of Public Health

text: Public health is politically paradoxical because its core conceptual components — the exercise of public authority and the promotion of population health — stand in practical tension that belies their theoretical promise. Across Western nations, public policymakers stand accused of failing properly to honor and support the crucial contributions that public health makes to the improvement of health outcomes and of overinvesting in acute medical care services, the need for which timely interventions in prevention and health promotion might have averted. The dramatic budgetary discrepancies in Western nations between the massive funds devoted to medical care and the minuscule sums allotted to public health are often taken as evidence that in such matters, political leaders are irrational (or perhaps uninformed, or captured by big-moneyed medical interests) and that good public policy would have epidemiologists and other public health experts running, or at least orchestrating, the show. This paper explores the sources of this tension between population health and political power within the concept of public health and seeks to show why these strains prove to be so durable, indeed irresolvable. The argument and evidence draw largely on the United States, but the supposition — yway, the hope — is that the analysis will also throw light on the politics of public health in other nations.


title: Plasma exudation and asthma

text: Several pieces of evidence support the view that exudation of plasma into the airway wall and into the airway lumen occurs in asthma. Vascular leakage of plasma results from inflammatory mediator-induced separation of endothelial cells in postcapillary venules belonging to the tracheobronchial circulation. Whereas proposed mediators of asthma induce reversible leakage, several antiasthma drugs exhibit antileakage effects in animals and humans. Potential consequences of plasma exudation are many. Mucosal/submucosal edema might contribute to airway hyperresponsiveness. Plasma exudate in the airway lumen in asthma may contribute to sloughing of epithelium, impairment of mucociliary transport, narrowing of small airways, and mucus plug formation. Exuded plasma may cause airway inflammation and constriction because of its content of powerful mediators, and chemoattractant factors and plasma proteins may condition the inflammatory cells abundant in asthmatic airways to release mediators in response to stimuli that otherwise would be innocuous to the cells. It is concluded that inflammatory stimulus-induced increase in macromolecular permeability of the tracheobronchial microvasculature and mucosa may be a significant pathogenetic mechanism in asthma and that the postcapillary venular endothelium and airway epithelium that regulate leakage of plasma are important effector cells in this disease.


The 2006 Hugh Rodman Leavell Lecture “Globalization, Poverty, and Health”


title: Dynamics analysis of a delayed virus model with two different transmission methods and treatments

text: In this paper, a delayed virus model with two different transmission methods and treatments is investigated. This model is a time-delayed version of the model in (Zhang et al. in Comput. Math. Methods Med. 2015:758362, 2015). We show that the virus-free equilibrium is locally asymptotically stable if the basic reproduction number is smaller than one, and by regarding the time delay as a bifurcation parameter, the existence of local Hopf bifurcation is investigated. The results show that time delay can change the stability of the endemic equilibrium. Finally, we give some numerical simulations to illustrate the theoretical findings.


title: Crimean–Congo haemorrhagic fever: transmission to visitors and healthcare workers

text: Crimean–Congo haemorrhagic fever is a viral haemorrhagic disease, mostly transmitted by tick bites or through contact with infected animal’s blood, and bodily fluids. Nosocomial infections were occasionally reported in healthcare settings. We report nosocomial cluster of Crimean–Congo haemorrhagic fever including the visitor with unknown transmission.


title: Mit neun Fragen der Ursache auf der Spur

text: Wenn einer eine Reise tut — dann kommt er möglicherweise mit einer fiebrigen Erkrankung zurück, speziell, wenn er sich in den Tropen aufgehalten hat. Bei der Suche nach der Ursache ist unverzügliches Handeln erforderlich, denn Krankheiten wie die Malaria können rasch zu einer lebensbedrohlichen Gefahr werden. Wie Sie in der Differenzialdiagnostik bei Fieber nach einer Tropenreise systematisch und möglichst schnell vorgehen, erläuterte der Tropenmediziner Dr. Fritz Holst aus Marburg. Neun entscheidende Fragen sollten Sie dabei nicht vergessen.


title: Lessons from SARS and H1N1/A: Employing a WHO–WTO forum to promote optimal economic-public health pandemic response

text: No formal system exists to review trade restrictions imposed during international public health emergencies rapidly. Failure to put one in place creates disincentives for surveillance and reporting, thereby undermining protection efforts. The 2003 SARS outbreak exposed weaknesses in global governance that caused uncoordinated public health and economic responses. New International Health Regulations (IHR), applied first during the 2009 H1N1 influenza outbreak, demonstrated improvement. Yet they failed to allow for management of public health emergencies in a way that balanced threats to health and those to economies and trade. Establishment of a joint WHO–WTO committee to adjudicate these conflicts might better achieve that balance.


Guest Editorial: Politics and health


title: Lactulose, Disaccharides and Colonic Flora: Clinical Consequences

text: Lactulose is one of the most frequently utilised agents in the treatment of constipation and hepatic encephalopathy because of its efficacy and good safety profile. The key to understanding the possible modes of action by which lactulose achieves its therapeutic effects in these disorders lies in certain pharmacological phenomena: (a) lactulose is a synthetic disaccharide that does not occur naturally; (b) there is no disaccharidase on the microvillus membrane of enterocytes in the human small intestine that hydrolyses lactulose; and (c) lactulose is not absorbed from the small intestine. Thus, the primary site of action is the colon in which lactulose is readily fermented by the colonic bacterial flora with the production of short-chain fatty acids and various gases. The purpose of this review is to focus on some pertinent basic aspects of the clinical pharmacology of lactulose and to discuss the possible mechanisms by which lactulose benefits patients with constipation and hepatic encephalopathy.


title: Sommergrippe: Mehr als ein Mythos!

text: Durchsucht man die deutschsprachige medizinische Literatur nach dem Begriff „Sommergrippe“, scheitert man kläglich. Jeder glaubt zu wissen, was damit gemeint ist, doch keiner schreibt darüber. Ist das überhaupt ein seriöses Thema?


When the world catches cold: Thinking with influenza


title: A North/South collaboration between two national public health institutes – A model for global health protection

text: Rapid international spread of emerging infections has increased interest in strategic collaborations, as they may be the best way to protect populations. Strategic collaborations can build capacity in less-resourced settings. As specialised institutions that provide a stable locus of expertise, continuity of experience, scientific knowledge, and appropriate human, technical, and financial resources, national public health institutes (NPHIs) are well-prepared to tackle public health challenges. We describe how a collaboration between the NPHIs of England and South Africa built a mutually beneficial professional relationship to help implement the WHO International Health Regulations, build capacity for health protection, and promote the exchange of information, advice, and expertise. We illustrate how this can be achieved in a mutually beneficial way.


title: Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

text: Viral and microbial constituents contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). In addition, intracellular viral double-stranded RNA is detected by two recently characterized DExD/H box RNA helicases, RIG-I and Mda-5. Both TLR-dependent and -independent pathways engage the IκB kinase (IKK) complex and related kinases TBK-1 and IKKɛ. Activation of the nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) transcription factor pathways are essential immediate early steps of immune activation; as a result, both pathways represent prime candidates for viral interference. Many viruses have developed strategies to manipulate NF-κB signaling through the use of multifunctional viral proteins that target the host innate immune response pathways. This review discusses three rapidly evolving areas of research on viral pathogenesis: the recognition and signaling in response to virus infection through TLR-dependent and -independent mechanisms, the involvement of NF-κB in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-κB pathway.


WFPHA: World Federation of Public Health Associations


title: Fremdblut sparende Maßnahmen

text: Fremdblut sparende Maßnahmen versprechen den Nutzen einer ausreichenden Anzahl von Sauerstoffträgern ohne die typischen Nachteile der allogener Bluttransfusion. Dennoch erlaubt nur die genaue Kenntnis dieser Verfahren einen für den Patienten effektiven und risikoarmen Einsatz. Im Folgenden werden Nutzen und Risiken des Einsatzes von Fremdblut, sowie Maßnahmen zur Verringerung allogener Transfusionen kritisch beleuchtet. Diese Maßnahmen können einerseits im restriktiven Einsatz von Fremdblut, andererseits in spezifischen Fremdblut sparenden Maßnahmen liegen. Darüber hinaus ist eine blutarme Operationstechnik entscheidend für das Einsparen von Fremdbluttransfusionen; dies soll jedoch hier nicht näher erläutert werden.


title: Smectic viral capsids and the aneurysm instability

text: The capsids of certain Archaea-infecting viruses undergo large shape changes, while maintaining their integrity against rupture by osmotic pressure. We propose that these capsids are in a smectic liquid crystalline state, with the capsid proteins assembling along spirals. We show that smectic capsids are intrinsically stabilized against the formation of localized bulges with non-zero Gauss curvature while still allowing for large-scale cooperative shape transformation that involves global changes in the Gauss curvature.


title: Chemopreventive Effects of Licorice and Its Components

text: Cancer is still a major health issue worldwide and identifying novel but safe compounds for prevention and treatment is a high priority. Licorice (Glycyrrhiza) is a perennial plant that is cultivated in many countries and has been reported to exert antioxidant, anti-inflammatory and anticancer effects. However, some components of licorice exert unwanted side effects and therefore identifying safer licorice components would be ideal. The anticancer activities of many of the licorice components appear to include cycle arrest, apoptosis induction, and general antioxidant effects. Commonly reported indirect protein targets important in tumorigenesis include many cell cycle-related proteins, apoptosis-associated proteins, MMP proteins, COX-2, GSK-β, Akt, NF-κB, and MAP kinases. Importantly, several licorice components were reported to directly bind to and inhibit the activities of PI3-K, MKK4, MKK7, JNK1, mTOR, and Cdk2, resulting in decreased carcinogenesis in several cell and mouse models with no obvious toxicity. This review focuses on specific components of licorice for which a direct protein target has been identified.


title: Performativity and a microbe: Exploring Mycobacterium bovis and the political ecologies of bovine tuberculosis

text: Mycobacterium bovis, the bacterium responsible for causing bovine tuberculosis (bTB) in cattle, displays what I call ‘microbial performativity’. Like many other lively disease-causing microorganisms, it has an agency which is difficult to contain, and there is a need for fresh thinking on the challenges of dealing with this slippery and indeterminate microbe. As a practising veterinary scientist who side-stepped mid-career into a parallel training in the social sciences to view bTB from an alternative perspective, I create an interdisciplinary coming-together where veterinary science converges with a political ecology of (animal) health influenced by science and technology studies (STS) and social science and humanities scholarship on performativity. This suitably hybridized nexus creates a place to consider the ecologies of a pathogen which could be considered as life out of control. I consider what this means for efforts to eradicate this disease through combining understandings from the published scientific literature with qualitative interview-based fieldwork with farmers, veterinarians and others involved in the statutory bTB eradication programme in a high incidence region of the UK. This study demonstrates the value of life scientists turning to the social sciences to re-view their familiar professional habitus—challenging assumptions, and offering alternative perspectives on complex problems.


title: Sequence Motifs Comparisons Establish a Functional Portrait of a Multifunctional Protein HC-Pro from Papaya Ringspot Potyvirus

text: Helper component proteinase (HC-Pro) is a multifunctional protein responsible for multiple molecular events in viral cycle. Here, we demonstrate that functional correlation of sequence motifs of HC-Pro is an important source to predict its role in deubiqutinylation pathway and rescuing viral proteins from degradation. The sequence of papaya ringspot viral HC-Pro was compared with respect to both inter and intea-species across different potyviruses. This study suggested that highly conserved domains involved in post transcriptional gene silencing (PTGS) suppression and proteolytic activity are essential functions in plant-virus cycle. In contrast, mechanisms primed for differentiation such as host specificity and virus replication are less conserved. Also, they contribute substantially to the differences among HC-Pro, derived from different potyviruses. The results obtained from this study provide a framework for new hypothesis and research directions in the area of differential role of potyviral HC-Pro.


title: EMS Disease Exposure, Transmission, and Prevention: a Review Article

text: PURPOSE OF REVIEW: This article aims to review recent literature regarding the risks of disease exposure to pre-hospital providers and the patients they serve, as well as the challenges they face in minimizing transmission and exposure. RECENT FINDINGS: Many studies continue to show poor compliance with consistent universal precautions, as well as proper hand hygiene. Vaccination rates are suboptimal despite attempts to encourage compliance. With the spread of multi-drug resistant organisms, new techniques of decontamination need to be investigated. SUMMARY: There remains a general lack of information and studies regarding the risks of disease exposure and transmission to EMS providers despite the significance hazards their profession can pose. However, there remains a continued theme throughout the majority of EMS and pre-hospital studies, demonstrating that hand washing and consistent use of personal protective equipment remains a persistent, preventable means of disease exposure and transmission.


Fortbildung in Zeiten von COVID-19


Schon junge Ärzte oft ausgebrannt: Internationaler Survey


Interesting times


title: A normative study of acronyms and acronym naming

text: Acronyms are an idiosyncratic part of our everyday vocabulary. Research in word processing has used acronyms as a tool to answer fundamental questions such as the nature of the word superiority effect (WSE) or which is the best way to account for word-reading processes. In this study, acronym naming was assessed by looking at the influence that a number of variables known to affect mainstream word processing has had in acronym naming. The nature of the effect of these factors on acronym naming was examined using a multilevel regression analysis. First, 146 acronyms were described in terms of their age of acquisition, bigram and trigram frequencies, imageability, number of orthographic neighbors, frequency, orthographic and phonological length, print-to-pronunciation patterns, and voicing characteristics. Naming times were influenced by lexical and sublexical factors, indicating that acronym naming is a complex process affected by more variables than those previously considered.


title: A modified turbulence model for simulating airflow aircraft cabin environment with mixed convection

text: The forced convection (air supply jet) and the natural convection (thermal plume of passenger) co-exist in an aircraft cabin simultaneously. Due to the notable difference of the Reynolds numbers for the two convection processes, the traditional RANS method can hardly simulate the forced/natural convection flows accurately at the same time. In addition, the large geometric ratio between the main air supply inlet and the whole cabin leads to difficulties in grid generation for the cabin space. An efficient computational model based on the standard k-e model is established to solve these problems. The coefficients in the dissipative equation are modified to compensate the enlarged numerical dissipation caused by coarse grid; meanwhile, the piecewise-defined turbulent viscosity is introduced to combine the forced and natural convection. The modified model is validated by available experimental results in a Boeing 737-200 mock-up. Furthermore, the unsteady characteristic of the aircraft cabin environment is obtained and analyzed. According to the frequency analysis, it turns out that the thermal plume is the main factor of the unsteady fluctuation in cabin. ELECTRONIC SUPPLEMENTARY MATERIAL: Electronic Supplementary Material (ESM): supplementary material is available in the online version of this article at 10.1007/s12273-020-0609-2.


ICAR 2011: Abstracts


Overview of Taiwan-Japan joint symposium (2SDP) on structural biology using X-ray crystallography and cryo-EM at the 2019 BSJ meeting.


title: Gender, Technology and Disability in the South

text: Asha Hans explores the impact of new technologies on women with disabilities, with a focus on women from developing countries. For women with disabilities, especially in developing countries, these new advances are critical not only to their future quality of life, but also their identity and very survival.


title: Fieber nach Tropenaufenthalt

text: Bei Fieber nach Tropenaufenthalt kommen eine Vielzahl möglicher Erkrankungen in Frage. Anhand der Anamnese und einfacher Basisuntersuchungen können Sie rasch die Schwere und Bedeutung (lebensbedrohlich? ansteckend?) der Erkrankung feststellen.


title: A discrete-time analog for coupled within-host and between-host dynamics in environmentally driven infectious disease

text: In this paper, we establish a discrete-time analog for coupled within-host and between-host systems for an environmentally driven infectious disease with fast and slow two time scales by using the non-standard finite difference scheme. The system is divided into a fast time system and a slow time system by using the idea of limit equations. For the fast system, the positivity and boundedness of the solutions, the basic reproduction number and the existence for infection-free and unique virus infectious equilibria are obtained, and the threshold conditions on the local stability of equilibria are established. In the slow system, except for the positivity and boundedness of the solutions, the existence for disease-free, unique endemic and two endemic equilibria are obtained, and the sufficient conditions on the local stability for disease-free and unique endemic equilibria are established. To return to the coupling system, the local stability for the virus- and disease-free equilibrium, and virus infectious but disease-free equilibrium is established. The numerical examples show that an endemic equilibrium is locally asymptotically stable and the other one is unstable when there are two endemic equilibria.


In diesen Fällen kann nun telefonisch eine AU ausgestellt werden


title: The mitochondrial genome of UK (non-native) Dikerogammarus haemobaphes (Amphipoda: Gammaridae) informs upon Dikerogammarus evolution, invasions and associated microparasites

text: The amphipod Dikerogammarus haemobaphes is a high-risk carrier of parasites that impact wildlife in its non-native range. Studies using the mitochondrial genes, Cytochrome Oxidase Sub-Unit 1 (cox1) and small-subunit ribosomal RNA gene (16S), provide some nucleotide detail for understanding the evolution and phylogeography of this species. Despite this, the origins of the invasion remain unknown, as do the origins of its parasites. This study provides the full annotated mitochondrial genome (15,460 bp) of D. haemobaphes, consisting of 2 rRNAs, 24 tRNAs and 14 protein coding genes. Mitochondrial genes from the UK isolate are compared to existing data on NCBI and are used in a concatenated phylogenetic approach and identify D. haemobaphes as an early member of the Gammaridae (Amphipoda). Viral, bacterial, protistan and microsporidian parasites are present across the Gammaridae, including D. haemobaphes, suggesting the ancestor of the Gammaridae harboured related diseases, and that further screening of amphipods is likely to reveal further microparasite diversity. This correlation suggests that other gammarid invaders have the potential to harbour a range of microparasites. The mitochondrial genome of this species will act a resource to facilitate our understanding of geneflow, disease epidemiology and evolutionary history in this invasion-disease model.


Abstracts of the 4th annual meeting of the German Society of Clinical Pharmacology and Therapy: Hannover, 14–17 September 1994


Abstracts - Scientific Exhibits


27th Congress of the European Society of Paediatric Radiology Munich, May 16–19, 1990: Abstracts


Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH)


Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V.


title: Infected teratoma of lower posterior mediastinum in a six-year-old boy

text: A six-year old boy presented with prolonged unexplained fever caused by an infected teratoma of the lower posterior mediastinum. Modern imaging, combining ultrasonography with computed tomography, enabled the correct diagnosis of topography, extension and nature of this rare lesion to be made and explained the clinical features. Follow-up CT showed regression of the abscess after antibiotics thus permitting elective surgery.


49th Annual Meeting Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie, Mainz, March 11-13, 2008


Symposium 3: Non-enzymatic biocatalysts in nature and biotechnology


38(th) EUROPEAN SOCIETY OF NEURORADIOLOGY Diagnostic and Interventional ANNUAL MEETING


European Nuclear Medicine Congress: August 14–17, 1984, Helsinki, Finland


Abstracts from the First International Conference on Heart Failure in Children and Young Adults


Bioluminescence, chemiluminescence


title: Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced

text: The collectin surfactant protein-D (SP-D) plays a significant role in innate immunity. Epidemiological studies described associations between single nucleotide polymorphisms (SNPs) of the human gene coding surfactant protein-D (SFTPD) and infectious pulmonary diseases. Studies on twins indicated very strong genetic dependence for serum levels of SP-D. The aim of this study was to determine the genetic influence of sequence variations within the SFTPD gene on the constitutional serum SP-D levels. We sequenced the 5′ untranslated region (5′UTR), the coding region and the 3′ region of the SFTPD gene of 32 randomly selected blood donors. Six validated SNPs were genotyped with sequence-specific probes (TaqMan 7000) in 290 German blood donors. Serum SP-D levels were analysed by ELISA, and the association of SFTPD haplotype estimates with the quantitative phenotype serum SP-D level was determined. One single SFTPD haplotype (allele frequency 13.53%) revealed a negative association with serum SP-D levels (P<0.0001). This was confirmed in a second prospectively collected group of blood donors (n=160, P=0.0034). The discovery of a frequent negative variant of the SFTPD gene provides a basis for genetic analysis of the function of SP-D in the resistance against pulmonary infections and inflammatory disorders in humans.


title: Imaging characteristics of hemophagocytic lymphohistiocytosis

text: BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. OBJECTIVE: To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH. MATERIALS AND METHODS: Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data. RESULTS: Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case. CONCLUSIONS: Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma.


title: Inflammation, Myocardial Dysfunction, and Mortality in Children With Septic Shock: An Observational Study

text: We aimed to investigate whether nuclear factor kappa-B activation, as evaluated by gene expression of its inhibitor (I-κBα) and cytokine serum levels, was associated with myocardial dysfunction and mortality in children with septic shock. Twenty children with septic shock were prospectively enrolled and grouped according to ejection fraction (EF) <45 % (group 1) or EF ≥45 % (group 2) on the first day after admission to the pediatric intensive care unit. No interventions were made. In the first day, patients from group 1 (n = 6) exhibited significantly greater tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10 plasma levels. However, I-κBα gene expression was not different in both groups. Mortality and number of complications were significantly greater in group 1. Patients who died had greater plasma concentrations of TNF-α. In conclusion, TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children, and TNF-α is associated with mortality.


title: Rotavirus gastroenteritis in infants and young children

text: The electronmicroscopic examination of stool samples from 18 infants and young children with gastroenteritis, hospitalized at the Clinic of Infectious Diseases in Prague, was carried out. In ten children rotavirus was found in the faeces and the bacteriological findings were negative. Rotavirus particles were aggregated by convalescent child sera and by normal human gamma globulin. The clinical picture was characterized by the sudden onset of vomiting and fever, in one case with febrile convulsions. Diarrhoea was watery and yellow-green, and usually persisted for four to five days. The condition of the children improved rapidly after rehydratation and a special diet. Older siblings, and in one family also adult members, were frequently affected.


Infection in Athletes


title: The Sore Throat: When to Investigate and When to Prescribe

text: Sore throats are most commonly due to infections, many of which are viral and do not require specifibrillationc treatment. Symptoms and signs of the common cold, influenza or croup, the occurrence of conjunctivitis in some adenoviral infections, generalised lymph-adenopathy and splenomegaly in glandular fever or the presence of vesicles characteristic of herpangina (Coxsackie A virus) or of herpes simplex infection, occasionally enable a clinical diagnosis and avoid the need for antibiotic therapy. In the case of treatable conditions a typical membrane may suggest diphtheria, a scarlatiniform rash infection due to Streptococcus pyogenes or to Corynebacterium haemolyticum, and a cherry-red epiglottis Haemophilus influenzae type b. Associated atypical pneumonia suggests infection with Mycoplasma pneumoniae or Chlamydia pneumoniae Pharyngitis due to Neisseria gonorrhoeae may be accompanied by infection at other sites or by other sexually transmitted diseases. Candidal infection, in the appropriate clinical circumstance, should suggest HIV infection. Surgical drainage is required in the case of peritonsillar or retropharyngeal abscess. Noninfectious cases of sore throat, e.g. thyroiditis, are relatively uncommon considerations in the differential diagnosis of acute febrile pharyngitis. The most common problem is to recognise streptococcal pharyngitis, which requires antibiotic treatment for 10 days to avoid the risk of rheumatic fever


title: The Use of Antiallergic and Antiasthmatic Drugs in Viral Infections of the Upper Respiratory Tract

text: Despite their frequency, upper respiratory tract infections (URTIs) constitute an area with few, if any, effective treatment remedies. Asthma and airway allergies share similar pathogenetic mechanisms to URTIs and it is not surprising, therefore, that agents used to treat allergic disorders have also been studied in URTIs. Their possible effects, limitations and hypothetical modes of action in URTIs are reviewed. In controlled clinical trials of satisfactory scientific standard, symptom reductions in both experimental rhinovirus infections and natural colds have occurred with topical anticholinergics, oral antihistamines and topical chromones. Future treatment alternatives for URTIs may include the intranasal anticholinergic ipratropium bromide, new nonsedating antihistamines and sodium cromoglycate (cromolyn sodium). The latter has a record of safety and an absence of adverse effects that would make it an attractive alternative for this common but not particularly serious condition in otherwise healthy individuals.