title: Eosinophilic alveolitis in BAL after lung transplantation

text: Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.


title: Endogene Lectine des Menschen und ihre Zuckerliganden: Zellbiologische und klinische Bedeutung*

text: Lectins are phylogenetically ancient proteins that have specific recognition and binding functions for complex carbohydrates of glycoconjugates, i. e., of glycoproteins, proteoglycans/glycosaminoglycans and glycolipids. This class of proteins mediates important processes of adhesion and communication both inside and outside cells. A large variety of lectins are expressed in the human organism. This article reviews the current knowledge of human lectins with a focus on biochemistry and pathobiochemistry (principles of protein glycosylation and defects of glycosylation as a basis of disease) and cell biology (protein sorting, exocytosis and endocytosis, apoptosis, cell adhesion, cell differentiation, and malignant transformation). The clinical significance of lectin-glycoconjugate interactions is described by example of inflammatory diseases, defects of immune defense, autoimmunity, infectious diseases, and tumor invasion/metastasis. Moreover, therapeutic perspectives of novel drugs that interfere with lectin-carbohydrate interactions are discussed.


title: 3D Printed Patient-Specific Acetabular Jig for Cup Placement in Total Hip Arthroplasty

text: INTRODUCTION: Acetabular cup placement is an important modifiable factor determining complication rates like aseptic loosening and hip dislocation related to faulty cup placement, which by standard method is largely dependent upon eyeballing and surgeon’s judgment. We evaluated a self-designed, low-cost, patient-specific acetabular jig to guide cup placement in total hip arthroplasty in comparison to conventional technique. METHODS: It was a prospective randomized control study. Thirty-six patients were categorized into group-A & group-B. In group-A, virtually designed acetabular jig was 3 Dimensional (3D) printed and used intra-operatively to guide cup placement. In group-B, the standard method of cup placement was used. Acetabular cup placement was evaluated on post-operative x-rays and compared between two groups. RESULTS: In group-A, angle of anteversion were significantly in centre of range of safe zone as compared to group B in which hip is maximally stable with more precision in creating hip centre as compared to group-B without any significant(p = 0.325) increase in surgical time or blood loss. CONCLUSION: Computed tomography (CT) scan based virtual pre-operative templating and cup placement guided by virtually designed, patient-specific acetabular jig is a low-cost tool with a short learning curve which can be designed and made available easily. It is a useful tool in decreasing chances of malpositioning of cup and recreates hip centre close to anatomical one especially in cases where anatomy has been distorted such as bony ankylosis and developmental dysplasia of hip.


title: Perioperative symptomatic venous thromboembolism after immediate chemoprophylaxis in patients with pelvic and lower-extremity fractures

text: The purpose of this study was to investigate the incidence of symptomatic venous thromboembolism (VTE) after chemoprophylaxis in patients with pelvic and lower-extremity fractures, and to identify risk factors for VTEs in this subgroup of patients. To detect VTE, multi-detector computed tomography (CT) angiography was performed. Of 363 patients assessed, the incidence of symptomatic VTE was 12.4% (45 patients), and the incidence of symptomatic PE was 5.2% (19 patients). For the risk-factor analysis, a higher Charlson comorbidity index (p = 0.037), and a history of external fixator application (p = 0.007) were associated with increased VTE risk. Among patients who had VTE, male sex (p = 0.017), and above-the-knee fractures (p = 0.035) were associated with increased pulmonary embolism (PE) risk. In conclusions, the incidence of VTE in post-traumatic patients is not low after chemoprophylaxis. Risk factors for VTE and PE are different among patients with pelvic and lower-extremity fractures.


title: Role of electrolyte abnormalities and unmeasured anions in the metabolic acid‐base abnormalities in dogs with parvoviral enteritis

text: BACKGROUND: The strong ion model (SIM) is an alternative paradigm in the characterization of acid‐base disturbances particularly in complex disorders. HYPOTHESIS/OBJECTIVES: To compare the acid‐base changes in dogs with parvoviral enteritis (PE) using the Henderson‐Hasselbalch (HH) approach, with 2 strong ion approaches. ANIMALS: Forty‐four dogs with PE, and 16 age‐matched control dogs. METHODS: Prospective controlled observational study. Acid‐base status was evaluated using the HH model, Fencl‐Stewart (FS) approach and a validated strong ion model (VDM). The acid‐base changes according to each model were classified and compared. Statistical correlations between pH, CO(2), and various SIM variables were performed, as well as between the sum of effects (SOE) of the SIM and the individual variables comprising the SOE. RESULTS: The HH model identified acid‐base disorders in 31/44 cases of which 16/31 were mixed with metabolic acidosis and concurrent respiratory alkalosis the most common (10/31). Using the FS approach, metabolic changes were present 36/42 cases, with changes in free water (FW), chloride, and unmeasured anions (UA) being the most prevalent. Both FW and UA correlated well with pH; however, UA were most consistently abnormal in severe acidemia. Similarly to the HH, the VDM detected acid‐base disturbances in 28/44 cases. Major contributors to the acid‐base changes were hyponatremia, hypochloremia, and A(tot) acidosis because of elevated globulins and increased UA. CONCLUSIONS AND CLINICAL IMPORTANCE: Acid‐base changes are common and complex in dogs with PE, and were easier to understand using a SIM paradigm. Increases in UA have not been documented in PE in dogs.


title: Immunity by ubiquitylation: a reversible process of modification

text: The conjugation of ubiquitin, a 76-amino-acid peptide, to a protein substrate provides a tag that either marks the labelled protein for degradation or modulates its function. The process of protein ubiquitylation — which is catalysed by coordinated enzymatic reactions that are mediated by enzymes known as E1, E2 and E3 — has an important role in the modulation of immune responses. Importantly, protein ubiquitylation is a reversible process, and removal of ubiquitin molecules is mediated by de-ubiquitylating enzymes: for example, A20, which has been implicated in the regulation of immune responses. In addition, the conjugation of ubiquitin-like molecules, such as ISG15 (interferon-stimulated protein of 15 kDa), to proteins is also involved in immune regulation. This Review covers recent progress in our understanding of protein ubiquitylation in the immune system.


Public–private partnerships boost research on neglected diseases


title: Protozoan genomics for drug discovery

text: Comparing the metabolic pathways of parasites and their hosts facilitates the identification of new drug targets.


Huitième congrès international de la Société de pathologie exotique, Vientiane, Laos, 25–28 janvier 2010: les défis sanitaires de l’Asie du Sud-Est


Effect of a behaviour-change intervention on hand washing with soap in India (SuperAmma): A Cluster-Randomised Trial: Source Citation: Biran A, Schmidt W, Varadharajan KS, Rajaraman D, Kumar R, Greenland K, et al. Lancet Glob Health 2014;2:E145–54.


title: Health biotechnology innovation on a global stage

text: With increasing globalization, infectious diseases are spreading faster than ever before, creating an urgent need for international collaboration. The rise of emerging economies has changed the traditional collaborative landscape and provided opportunities for more diverse models of collaboration involving developing countries, including North–South, South–South and North–South–South partnerships. Here, we discuss how developing countries can partner with other nations to address their shared health problems and to promote innovation. We look specifically at what drives collaborations and at the challenges that exist for them, and we propose actions that can strengthen these partnerships. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro2492) contains supplementary material, which is available to authorized users.


Case Reports


title: Twitter sentiment classification for measuring public health concerns

text: An important task of public health officials is to keep track of health issues, such as spreading epidemics. In this paper, we are addressing the issue of spreading public concern about epidemics. Public concern about a communicable disease can be seen as a problem of its own. Keeping track of trends in concern about public health and identifying peaks of public concern are therefore crucial tasks. However, monitoring public health concerns is not only expensive with traditional surveillance systems, but also suffers from limited coverage and significant delays. To address these problems, we are using Twitter messages, which are available free of cost, are generated world-wide, and are posted in real time. We are measuring public concern using a two-step sentiment classification approach. In the first step, we distinguish Personal tweets from News (i.e., Non-Personal) tweets. In the second step, we further separate Personal Negative from Personal Non-Negative tweets. Both these steps consist themselves of two sub-steps. In the first sub-step (of both steps), our programs automatically generate training data using an emotion-oriented, clue-based method. In the second sub-step, we are training and testing three different Machine Learning (ML) models with the training data from the first sub-step; this allows us to determine the best ML model for different datasets. Furthermore, we are testing the already trained ML models with a human annotated, disjoint dataset. Based on the number of tweets classified as Personal Negative, we compute a Measure of Concern (MOC) and a timeline of the MOC. We attempt to correlate peaks of the MOC timeline to peaks of the News (Non-Personal) timeline. Our best accuracy results are achieved using the two-step method with a Naïve Bayes classifier for the Epidemic domain (six datasets) and the Mental Health domain (three datasets).


title: Plaudits for microbiologists in 2008

text: Prizes for scientific endeavour can inspire researchers and the public alike. Nature Reviews Microbiology investigates which microbiologists were winners in 2008.


title: Long live structural biology

text: Two camps continue to evolve in the field of structural biology—a 'systems-oriented' camp, which studies proteins or complexes carefully one system at a time, and a 'discovery-oriented' one, which studies proteins of entire families, pathways or genomes. The end goals of both camps are the same: to decipher the atomic-resolution structures and mechanisms of biological macromolecules and understand them in the context of the living cell.


title: Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

text: In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19(+) acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.


title: From data to models

text: Data on the movement of people becomes ever more detailed, but robust models explaining the observed patterns are still needed. Mapping the problem onto a 'network of networks' could be a promising approach.


title: Dilated cardiomyopathy

text: Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter–defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.


The necessity of molecular diagnostics for avian flu


The year of bird flu


title: Viral RNA pseudoknots: versatile motifs in gene expression and replication

text: RNA pseudoknots are structural elements found in almost all classes of RNA. First recognized in the genomes of plant viruses, they are now established as a widespread motif with diverse functions in various biological processes. This Review focuses on viral pseudoknots and their role in virus gene expression and genome replication. Although emphasis is placed on those well defined pseudoknots that are involved in unusual mechanisms of viral translational initiation and elongation, the broader roles of pseudoknots are also discussed, including comparisons with relevant cellular counterparts. The relationship between RNA pseudoknot structure and function is also addressed. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro1704) contains supplementary material, which is available to authorized users.


Letter from the Editors


title: Expression profiling of microRNAs in lipopolysaccharide-induced acute lung injury after hypothermia treatment

text: We investigated the expression profiles of miRNAs in acute lung injury (ALI) rats after hypothermia treatment. ALI rats were induced with lipopolysaccharide (LPS) and maintained with hypothermia (HT) or normothermia (NT) for 6 hours. HT attenuated inflammatory cell infiltration in the lung and improved biochemical indicators of multi-organ dysfunction. Nineteen miRNAs were significantly differentially expressed in the HT group compared with the NT group. miR-142, miR-98, miR-541, miR-503, miR-653, miR- 223, miR-323 and miR-196b exhibited opposite patterns of expression between the two groups. These dysregulated miRNAs were mainly involved in the immune and inflammatory response on functional annotation analyses. This study shows that HT has lung protective effects and influences expression profiles of miRNAs in ALI. And dysregulated miRNAs after HT modulate the immune and inflammation in ALI. These results suggest that dysregulated miRNAs play a role in the mechanism of the lung protective effects of HT in ALI.


title: An Infant with Interstitial Lung Disease

text: Interstitial lung disease in infants, unlike older children and adults, has diverse etiology, including infective, metabolic, autoimmune, genetic, malignant and idiopathic causes. Clinical recognition of the interstitial pattern of lung involvement is important as the etiology and management is entirely different from that of recurrent or chronic lung parenchymal pathologies. We discuss the clinical and pathological findings of an infant with interstitial pneumonia, who succumbed to hospital-acquired sepsis.


title: Cloning, expression and characterization of serine palmitoyltransferase (SPT)-like gene subunit (LCB2) from marine Emiliania huxleyi virus (Coccolithovirus)

text: The authors have isolated and characterized a novel serine palmitoyltransferase (SPT)-like gene in marine Emiliania huxleyi virus (EhV-99B1). The open-reading frame (ORF) of EhV99B1-SPT encoded a protein of 496 amino acids with a calculated molecular mass of 96 kDa and Ip 6.01. The results of sequence analysis showed that there was about 31%–45% identity in amino acid sequence with other organisms. The maximum likelihood phylogenetic tree suggested that the EhV99B1-SPT gene possibly horizontally transferred from the eukaryote. Hydrophobic profiles of deduced amino acid sequences suggested a hydrophobic, globular and membrane-associated protein with five transmembrane domains (TMDs) motifs. Several potential N-linked glycosylation sites were presented in SPT. These results suggested that EhV99B1-SPT was an integral endoplasmic reticulum membrane protein. Despite lower sequence identity, the secondary and three-dimensional structures predicted showed that the “pocket” structure element composed of 2α-helices and 4β-sheets was the catalytic center of this enzyme, with a typical conserved “TFTKSFG” active site in the N-terminal region and was very close to those of prokaryotic organisms. However, the N-terminal domain of EhV99B1-SPT most closely resembled the LCB2 catalysis subunit and the C-terminal domain most closely resembled the LCB1 regulatory subunit of other organisms which together formed a spherical molecule. This “chimera” was highly similar to the prokaryotic homologous SPT. For a functional identification, the EhV99B1-LCB2 subunit gene was expressed in Escherichia coli, which resulted in significant accumulation of new sphingolipid in E. coli cells.


China approves first gene therapy


title: Molecular mechanisms of translational control

text: Translational control is widely used to regulate gene expression. This mode of regulation is especially relevant in situations where transcription is silent or when local control over protein accumulation is required. Although many examples of translational regulation have been described, only a few are beginning to be mechanistically understood. Instead of providing a comprehensive account of the examples that are known at present, we discuss instructive cases that serve as paradigms for different modes of translational control.


title: Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota homeostasis

text: Inflammasome signalling is an emerging pillar of innate immunity and has a central role in the regulation of gastrointestinal health and disease. Activation of the inflammasome complex mediates both the release of the pro-inflammatory cytokines IL-1β and IL-18 and the execution of a form of inflammatory cell death known as pyroptosis. In most cases, these mediators of inflammation provide protection against bacterial, viral and protozoal infections. However, unchecked inflammasome activities perpetuate chronic inflammation, which underpins the molecular and pathophysiological basis of gastritis, IBD, upper and lower gastrointestinal cancer, nonalcoholic fatty liver disease and obesity. Studies have also highlighted an inflammasome signature in the maintenance of gut microbiota and gut–brain homeostasis. Harnessing the immunomodulatory properties of the inflammasome could transform clinical practice in the treatment of acute and chronic gastrointestinal and extragastrointestinal diseases. This Review presents an overview of inflammasome biology in gastrointestinal health and disease and describes the value of experimental and pharmacological intervention in the treatment of inflammasome-associated clinical manifestations.


title: Standing up to infectious disease

text: Despite major advances in dissecting how pathogens cause disease and the development of treatments to combat infection, infectious diseases remain a major cause of death today. This month’s issue includes a special ‘Focus on Infectious Disease’, which highlights efforts to develop new ways to prevent, detect and treat infections.


title: RNAi tackles a sexually transmitted disease

text: RNA therapy is effective against Herpes simplex virus-2 in mice.


title: DNA vaccines—back in the saddle again?

text: A promising new horse vaccine may reignite enthusiasm for DNA vaccine technology in designing prophylactics against infectious disease. Kendall Powell reports.


title: Mathematical analysis of swine influenza epidemic model with optimal control

text: A deterministic model is designed and used to analyze the transmission dynamics and the impact of antiviral drugs in controlling the spread of the 2009 swine influenza pandemic. In particular, the model considers the administration of the antiviral both as a preventive as well as a therapeutic agent. Rigorous analysis of the model reveals that its disease-free equilibrium is globally asymptotically stable under a condition involving the threshold quantity-reproduction number [Formula: see text] . The disease persists uniformly if [Formula: see text] and the model has a unique endemic equilibrium under certain condition. The model undergoes backward bifurcation if the antiviral drugs are completely efficient. Uncertainty and sensitivity analysis is presented to identify and study the impact of critical model parameters on the reproduction number. A time dependent optimal treatment strategy is designed using Pontryagin’s maximum principle to minimize the treatment cost and the infected population. Finally the reproduction number is estimated for the influenza outbreak and model provides a reasonable fit to the observed swine (H1N1) pandemic data in Manitoba, Canada, in 2009.


title: Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials

text: Long-term diabetes increases the likelihood of developing secondary damage to numerous systems, and these complications represent a substantial cause of morbidity and mortality. Establishing the causes of diabetes remains the key step towards eradicating the disease, but the prevention and amelioration of diabetic complications is equally important for the millions of individuals who already have the disease or are likely to develop it before prophylaxis or a cure become routinely available. In this Review, we focus on four common complications of diabetes, discuss the range of pathologies that are precipitated by hyperglycaemia and highlight emerging targets for therapeutic intervention.


title: Visualization of macromolecular structures

text: Structural biology is rapidly accumulating a wealth of detailed information about protein function, binding sites, RNA, large assemblies and molecular motions. These data are increasingly of interest to a broader community of life scientists, not just structural experts. Visualization is a primary means for accessing and using these data, yet visualization is also a stumbling block that prevents many life scientists from benefiting from three-dimensional structural data. In this review, we focus on key biological questions where visualizing three-dimensional structures can provide insight and describe available methods and tools. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmeth.1427) contains supplementary material, which is available to authorized users.


title: Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs

text: Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells. Accelerated clearance of virus by group 1 ILCs precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and diminished resistance to colonization. In sum, FRCs act as an 'on-demand' immunological 'rheostat' by restraining activation of group 1 ILCs and thereby preventing immunopathological damage in the intestine. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.3566) contains supplementary material, which is available to authorized users.


title: Furosemide infusion in children with dengue fever and hypoxemia

text: OBJECTIVES: To study the role of furosemide infusion in the management of Acute respiratory distress syndrome (ARDS) associated with dengue fever. METHODS: Children between the ages of 1 month to 18 years, who fulfilled the WHO clinical criteria for dengue infection and American European Consensus Criteria criteria for ARDS with Dengue IgM positivity, were evaluated. Patients were studied as group D (receiving diuretic therapy alone) and group B (both ventilation and diuretics), and compared to a historical control group V (ventilation alone). Furosemide infusion was administered at 0.05–0.1 mg/kg/hour for 48 hours, maintaining a urine output of 2–4 mL/kg/hour. RESULTS: There was a significant difference in survival in the three groups. Significant difference was noted between pre- and postintervention arterial blood gases with respect to PCO(2) (P=0.02), pO(2) (P=0.003), PaO(2)/FaO(2) ratio (P<0.001) and alveolar-arteriolar oxygen gradient (P=0.002). CONCLUSION: Diuretic infusion improves outcome in dengue with ARDS.


title: Leadership in public health

text: The modern public health model for leadership will unlikely be the omniscient figure with easy answers.51 Rather the public health leader of the future may well be the transcendent, collaborative «servant leader»(50,52) who knits and aligns disparate voices together behind a common mission. They pinpoint passion and compassion, promote servant leadership, acknowledge the unfamiliar, the ambiguous, and the paradoxical, communicate succinctly to reframe, and understand the «public» part of public health leadership. By working between and above the levels of leadership of self, others and organizations, these transcendent leaders can ultimately shift the paradigm from «no hope» to «new hope» and create a renewed sense of community. Such leadership will be vital as the 21st century progresses. Beginning the journey to new hope may start by motivating underdogs who nurture the spirit, discover a passion to serve, cultivate interdependence, and create uncommon bonds. These emerging leaders can tap into their unique talents, passion, and compassion to promote a mission of «the highest attainable standard of health» for all, in every community.


Coronavirus controversy


title: Tissue-specific immunopathology during malaria infection

text: Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur. Here, we give an overview of the recent progress that has been made in understanding tissue-specific immunopathology during Plasmodium infection. As knowledge on tissue-specific host–parasite interactions accumulates, better treatment modalities and targets may emerge for intervention in malaria disease. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2017.138) contains supplementary material, which is available to authorized users.


9(e) Congrès international francophone « Transitions épidémiologiques en Afrique : quelles réponses des systèmes de santé ? » — Résumés des communications orales: Organisé par la Société de pathologie exotique en partenariat avec la Société médicale d’Afrique Noire de langue française, UCAD 2 Dakar, Sénégal — 12–14 novembre 2013 Contact: socpatex@pasteur.fr


Synthetic DNA firms embrace hazardous agents guidance but remain wary of automated 'best-match'


Tracking down MERS coronavirus


title: Challenges and approaches for the development of safer immunomodulatory biologics

text: Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions — including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity — pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd3974) contains supplementary material, which is available to authorized users.


title: 2009 Pandemic influenza in India

text: Pandemic-09-H1N1 virus caused the pandemic starting in the second quarter of 2009. The world was prepared to face the pandemic since it was anticipated for over one decade. Most countries, including India, had made detailed pandemic preparedness plans well ahead of its actual occurrence. The infection rapidly spread to the whole country within 2-3 months. The national tactics were to slow down its importation through international air travelers and to slow down its spread in cities and major towns. More than 75% of all infected persons were urban dwellers, suggesting that efforts were concentrated in urban communities. In general the illness of pandemic influenza has been similar to endemic/seasonal influenza; however, there is insufficient epidemiological and clinical data on the latter. We hope that the unprecedented experience of managing the pandemic will encourage the Government of India to plan to confront endemic/seasonal influenza more systematically. The pandemic seems to have reached a peak in September/October and has been on the decline since then.


CORRECTIONS


In the News


title: Mechanisms, biomarkers and targets for adult-onset Still’s disease

text: Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in all adult age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications, AoSD is an unsolved challenge for clinicians with limited therapeutic options. This Review provides a comprehensive insight into the complex and heterogeneous nature of AoSD, describing biomarkers of the disease and its progression and the cytokine signalling pathways that contribute to disease. The efficacy and safety of biologic therapeutic options are also discussed, and guidance for treatment decisions is provided. Improving the approach to AoSD in the future will require much closer cooperation between paediatric and adult rheumatologists to establish common diagnostic strategies, treatment targets and goals.


title: The Behavior of Bacteria Designed for Biodegradation

text: Mineralization of organic molecules by microbes is essential for the carbon cycle to operate. The massive mobilization of compounds stored in natural resources, or the introduction of xenobiotics into the biosphere, leads to unidirectional fluxes, which result in the persistance of a number of chemicals in the biosphere, and thus constitute a source of pollution. Molecular biology offers the tools to optimize the biodegradative capacities of microorganisms, accelerate the evolution of “new” activities, and construct totally “new” pathways through the assemblage of catabolic segments from different microbes. Although the number of genetically engineered microbes (GEMs) for potential use in biodegradation is not large, these recombinant microbes function in microcosms according to their design. The survival and fate of recombinant microbes in different ecological niches under laboratory conditions is similar to what has been observed for the unmodified parental strains. rDNA, both on plasmids and on the host chromosome, is usually stably inherited by GEMs. The potential lateral transfer of rDNA from the GEMs to other microbes is significantly diminished, though not totally inhibited, when rDNA is incorporated on the host chromosome. The behavior and fate of GEMs can be predicted more accurately through the coupling of regulatory circuits that control the expression of catabolic pathways to killing genes, so that the GEMs survive in polluted environments, but die when the target chemical is eliminated.


title: Aptamers as therapeutics

text: Nucleic acid aptamers can be selected from pools of random-sequence oligonucleotides to bind a wide range of biomedically relevant proteins with affinities and specificities that are comparable to antibodies. Aptamers exhibit significant advantages relative to protein therapeutics in terms of size, synthetic accessibility and modification by medicinal chemistry. Despite these properties, aptamers have been slow to reach the marketplace, with only one aptamer-based drug receiving approval so far. A series of aptamers currently in development may change how nucleic acid therapeutics are perceived. It is likely that in the future, aptamers will increasingly find use in concert with other therapeutic molecules and modalities.


title: Clinical profile and outcome of swine flu in Indian children

text: OBJECTIVE: To describe the clinical characteristics and outcome of Indian children infected with 2009 H1N1 influenza virus. STUDY DESIGN: Retrospective chart review. SETTING: Outpatient department and hospitalized patients in a tertiary care hospital. METHODS: Clinical details of 85 children (positive for the 2009 H1N1 virus infection tested by real-time reverse-transcriptase-polymerase-chain-reaction assay) were analyzed from medical charts. RESULTS: Of the 85 (55 boys) children positive for 2009 H1N1 virus infection, 64.7% were between 5 years to 16 years, and 35.3% were below 5 years age. The mean age of these children was 7.5±3.5 yr. Contact history was positive only in 22 (26%) cases. High grade fever was the most common symptom, followed by cough and rhinorrhea. Twenty-nine (34%) patients had an underlying co-morbid condition. Of the 34 patients who underwent chest radiography during evaluation, 18 children (52.9%) had findings consistent with lower respiratory tract infection. Antiviral therapy was initiated in 76 patients. Hospitalization was required in 30 (35.3%) children. Risk factors for hospitalization included underlying co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph. Mean length of hospitalization was 131±76 hours, irrespective of underlying disease. Three children developed Acute Respiratory Distress Syndrome and died. CONCLUSIONS: Clinical features and routine laboratory investigations in children with swine origin influenza were non-specific. Children with co-morbid condition, respiratory distress, vomiting, wheezing, diarrhea, hypotension and infiltrates/consolidation on chest radiograph were at higher risk of hospitalization.


Infectious diseases: Vaccine for Middle East respiratory syndrome.


New coronavirus


title: Deployment of new biotechnologies in plant breeding

text: The first crops obtained through new plant breeding techniques are close to commercialization. Regulatory issues will determine the adoption of the techniques by breeders. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nbt.2142) contains supplementary material, which is available to authorized users.


FDA User Fees Gain Momentum


Vox populi and public policy: why should we care?


title: Ebola virus is unlikely to become endemic in West Africa

text: Concern over Ebola becoming endemic in West Africa has appeared in the medical and lay media. Routes of transmission, rates of viral evolution, suitability of humans as hosts and rarity of spillover events make this very unlikely. Without evidence that endemic Ebola is likely, ending epidemics should remain the focus.


title: “On the bat’s back I do fly”

text: Two recent studies provide new insights into bat virus spillover.


title: Synthetic biology

text: Synthetic biologists come in two broad classes. One uses unnatural molecules to reproduce emergent behaviours from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that function unnaturally. Either way, a synthetic goal forces scientists to cross uncharted ground to encounter and solve problems that are not easily encountered through analysis. This drives the emergence of new paradigms in ways that analysis cannot easily do. Synthetic biology has generated diagnostic tools that improve the care of patients with infectious diseases, as well as devices that oscillate, creep and play tic-tac-toe.


Imaging of lung inflammation during severe influenza A: H1N1


Focus: SARS


title: HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation

text: Hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is a multi-transmembrane protein, but little is known about how NS4B contributes to HCV replication and tumorigenesis. Its C-terminal domain (CTD) has been shown to associate with intracellular membrane, and we have previously shown that NS4B CTD contains a class I PDZ-binding motif (PBM). Here, we demonstrated that NS4B PBM interacts with the PDZ-containing tumor suppressor protein, Scribble, using immunofluorescence and co-immunoprecipitation assays, and this interaction requires at least three contiguous PDZ domains of Scribble. In addition, NS4B PBM specifically induced Scribble degradation by activating the proteasome-ubiquitin pathway. Similar Scribble degradation was also observed in HCV-infected cells, suggesting NS4B could work in the context of HCV. Finally, NS4B PBM mutants showed reduced colony formation capacity compared with its wild-type counterpart, indicating that NS4B PBM plays important roles in NS4B-mediated cell transformation. Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation.


Minimaxing risk


title: Norbert Bischofberger

text: Norbert Bischofberger, former CSO of Gilead, discusses antiviral opportunities, Gilead's pivot to oncology and the need for a societal discussion of drug costs.


title: Hendra and Nipah viruses: different and dangerous

text: Hendra virus and Nipah virus are highly pathogenic paramyxoviruses that have recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These features led to their classification into the new genus Henipavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. This review provides an overview of henipaviruses and the types of infection they cause, and describes how studies on the structure and function of henipavirus proteins expressed from cloned genes have provided insights into the unique biological properties of these emerging human pathogens.


title: Prognostic and predictive enrichment in sepsis

text: Sepsis is a heterogeneous disease state that is both common and consequential in critically ill patients. Unfortunately, the heterogeneity of sepsis at the individual patient level has hindered advances in the field beyond the current therapeutic standards, which consist of supportive care and antibiotics. This complexity has prompted attempts to develop a precision medicine approach, with research aimed towards stratifying patients into more homogeneous cohorts with shared biological features, potentially facilitating the identification of new therapies. Several investigators have successfully utilized leukocyte-derived mRNA and discovery-based approaches to subgroup patients on the basis of biological similarities defined by transcriptomic signatures. A critical next step is to develop a consensus sepsis subclassification system, which includes transcriptomic signatures as well as other biological and clinical data. This goal will require collaboration among various investigative groups, and validation in both existing data sets and prospective studies. Such studies are required to bring precision medicine to the bedside of critically ill patients with sepsis.


title: Macrophage migration inhibitory factor: a regulator of innate immunity

text: For more than a quarter of a century, macrophage migration inhibitory factor (MIF) has been a mysterious cytokine. In recent years, MIF has assumed an important role as a pivotal regulator of innate immunity. MIF is an integral component of the host antimicrobial alarm system and stress response that promotes the pro-inflammatory functions of immune cells. A rapidly increasing amount of literature indicates that MIF is implicated in the pathogenesis of sepsis, and inflammatory and autoimmune diseases, suggesting that MIF-directed therapies might offer new treatment opportunities for human diseases in the future.


title: Toll-like receptors in systemic autoimmune disease

text: Toll-like receptors (TLRs) have a crucial role in the early detection of pathogen-associated molecular patterns and the subsequent activation of the adaptive immune response. Whether TLRs also have an important role in the recognition of endogenous ligands has been more controversial. Numerous in vitro studies have documented activation of both autoreactive B cells and plasmacytoid dendritic cells by mammalian TLR ligands. The issue of whether these in vitro observations translate to an in vivo role for TLRs in either the initiation or the progression of systemic autoimmune disease is a subject of intense research; data are beginning to emerge showing that this is the case.


Cattle engineered to produce human antibodies against coronavirus


title: Community engagement

text: Crowdsourcing efforts, such as those involved in the Escherichia coli O104 outbreak and, most recently, ash dieback disease, reflect a new era of community engagement in genomic analyses.


title: Mechanisms of disease: pulmonary arterial hypertension

text: Our understanding of, and approach to, pulmonary arterial hypertension has undergone a paradigm shift in the past decade. Once a condition thought to be dominated by increased vasoconstrictor tone and thrombosis, pulmonary arterial hypertension is now seen as a vasculopathy in which structural changes driven by excessive vascular cell growth and inflammation, with recruitment and infiltration of circulating cells, play a major role. Perturbations of a number of molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, that may underlie the pathogenesis of the disease. Elucidating their contribution to the pathophysiology of pulmonary arterial hypertension could offer new drug targets. The role of progenitor cells in vascular repair is also under active investigation. The right ventricular response to increased pressure load is recognized as critical to survival and the molecular mechanisms involved are attracting increasing interest. The challenge now is to integrate this new knowledge and explore how it can be used to categorize patients by molecular phenotype and tailor treatment more effectively.


Conclusions: promoting biotechnology innovation in developing countries


title: Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity

text: Vaccination has achieved remarkable successes in the control of childhood viral diseases. To control emerging infections, however, vaccines will need to be delivered to older individuals who, unlike infants, probably have had prior infection or vaccination with related viruses and thus have cross-reactive antibodies against the vaccines. Whether and how these cross-reactive antibodies impact live attenuated vaccination efficacy is unclear. Using an open-label randomized trial design, we show that subjects with a specific range of cross-reactive antibody titres from a prior inactivated Japanese encephalitis vaccination enhanced yellow fever (YF) immunogenicity upon YF vaccination. Enhancing titres of cross-reactive antibodies prolonged YF vaccine viraemia, provoked greater pro-inflammatory responses, and induced adhesion molecules intrinsic to the activating Fc-receptor signalling pathway, namely immune semaphorins, facilitating immune cell interactions and trafficking. Our findings clinically demonstrate antibody-enhanced infection and suggest that vaccine efficacy could be improved by exploiting cross-reactive antibodies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmicrobiol.2016.164) contains supplementary material, which is available to authorized users.


title: Scientific barriers to developing vaccines against avian influenza viruses

text: The increasing number of reports of direct transmission of avian influenza viruses to humans underscores the need for control strategies to prevent an influenza pandemic. Vaccination is the key strategy to prevent severe illness and death from pandemic influenza. Despite long-term experience with vaccines against human influenza viruses, researchers face several additional challenges in developing human vaccines against avian influenza viruses. In this Review, we discuss the features of avian influenza viruses, the gaps in our understanding of infections caused by these viruses in humans and of the immune response to them that distinguishes them from human influenza viruses, and the current status of vaccine development.


title: Fluorine makes a difference

text: Introducing fluorine into the chemical formula of self-assembling supramolecular systems usually makes for more stable and robust lattices. Now a dendron molecule has been found for which fluorination brings about a change in the self-assembly motif and an unexpected supramolecular architecture.


title: Who's who in biotech

text: Nature Biotechnology's readers select some of biotech's most remarkable and influential personalities from the past 10 years.


title: Viral shape-shifting: norovirus evasion of the human immune system

text: Noroviruses are the most common cause of food-borne gastroenteritis worldwide, and explosive outbreaks frequently occur in community settings, where the virus can immobilize large numbers of infected individuals for 24–48 hours, making the development of effective vaccines and antiviral therapies a priority. However, several challenges have hampered therapeutic design, including: the limitations of cell culture and small-animal model systems; the complex effects of host pre-exposure histories; differential host susceptibility, which is correlated with blood group and secretor status; and the evolution of novel immune escape variants. In this Review, we discuss the molecular and structural mechanisms that facilitate the persistence of noroviruses in human populations.


67TH ASMS Conference on Mass Spectrometry and Allied Topics.


title: Anthropocène et viroses émergentes

text: We propose to bring together the new geologic concept of Anthropocene and its consequences on our environment with the observed increasing emergence of new viruses — a pathogen for both humans and animals, mainly since the mid of the twentieth century.


title: The interplay of extracellular matrix and microbiome in urothelial bladder cancer

text: Many pathological changes in solid tumours are caused by the accumulation of genetic mutations and epigenetic molecular alterations. In addition, tumour progression is profoundly influenced by the environment surrounding the transformed cells. The interplay between tumour cells and their microenvironment has been recognized as one of the key determinants of cancer development and is being extensively investigated. Data suggest that both the extracellular matrix and the microbiota represent microenvironments that contribute to the onset and progression of tumours. Through the introduction of omics technologies and pyrosequencing analyses, a detailed investigation of these two microenvironments is now possible. In urological research, assessment of their dysregulation has become increasingly important to provide diagnostic, prognostic and predictive biomarkers for urothelial bladder cancer. Understanding the roles of the extracellular matrix and microbiota, two key components of the urothelial mucosa, in the sequelae of pathogenic events that occur in the development and progression of urothelial carcinomas will be important to overcome the shortcomings in current bladder cancer treatment strategies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrurol.2015.292) contains supplementary material, which is available to authorized users.


Chinese vaccine developers gain WHO imprimatur


title: Novel RAAS agonists and antagonists: clinical applications and controversies

text: The renin–angiotensin–aldosterone system (RAAS) regulates blood pressure homeostasis and vascular injury and repair responses. The RAAS was originally thought to be an endocrine system critically important in regulating blood pressure homeostasis. Yet, important local forms of the RAAS have been described in many tissues, which are mostly independent of the systemic RAAS. These systems have been associated with diverse physiological functions, but also with inflammation, fibrosis and target-organ damage. Pharmacological modulation of the RAAS has brought about important advances in preventing morbidity and mortality associated with cardiovascular disease. Yet, traditional RAAS blockers such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) only reduce the risk of disease progression in patients with established cardiovascular or renal disease by ∼20% compared with other therapies. As more components of the RAAS are described, other potential therapeutic targets emerge, which could provide improved cardiovascular and renal protection beyond that provided by an ACE inhibitor or ARB. This Review summarizes the present and future pharmacological manipulation of this important system. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrendo.2015.6) contains supplementary material, which is available to authorized users.


title: Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A(2)

text: A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A(2) (hnps-PLA(2)) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA(2) complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The application of structure-based drug design has made possible improvements in the binding of this screening lead to the enzyme by nearly three orders of magnitude. Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA(2).


title: Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus

text: Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.


title: Chemokine receptors: multifaceted therapeutic targets

text: Chemokines and their receptors are involved in the pathogenesis of diseases ranging from asthma to AIDS. Chemokine receptors are G-protein-coupled serpentine receptors that present attractive tractable targets for the pharmaceutical industry. It is only ten years since the first chemokine receptor was discovered, and the rapidly expanding number of antagonists holds promise for new medicines to combat diseases that are currently incurable. Here, I focus on the rationale for developing antagonists of chemokine receptors for inflammatory disorders and AIDS, and the accumulating evidence that favours this strategy despite the apparent redundancy in the chemokine system.


Case reports


title: Ace revisited: A new target for structure-based drug design

text: Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. However, the use of these ACE inhibitors, which were developed in the late 1970s and early 1980s, is hampered by common side effects. Moreover, we now know that ACE actually consists of two parts (called the N- and C-domains) that have different functions. Therefore, the design of specific domain-selective ACE inhibitors is expected to produce next-generation drugs that might be safer and more effective. Here we discuss the structural features of current inhibitors and outline how next-generation ACE inhibitors could be designed by using the three-dimensional molecular structure of human testis ACE. The ACE structure provides a unique opportunity for rational drug design, based on a combination of in silico modelling using existing inhibitors as scaffolds and iterative lead optimization to drive the synthetic chemistry.


Biosecurity with 'bio-sense'


title: Glycan microarray technologies: tools to survey host specificity of influenza viruses

text: New technologies are urgently required for rapid surveillance of the current H5N1 avian influenza A outbreaks to gauge the potential for adaptation of the virus to the human population, a crucial step in the emergence of pandemic influenza virus strains. Owing to the species-specific nature of the interaction between the virus and host glycans, attention has recently focused on novel glycan array technologies that can rapidly assess virus receptor specificity and the potential emergence of human-adapted H5N1 viruses.


title: A family of macrodomain proteins reverses cellular mono-ADP-ribosylation

text: ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or other stresses. Poly-ADPr-glycohydrolase readily reverses poly-ADP-ribosylation induced by the DNA-damage sensor PARP1 and other enzymes, but it does not remove the most proximal ADPr linked to the target amino acid. Searches for enzymes capable of fully reversing cellular mono-ADP-ribosylation back to the unmodified state have proved elusive, which leaves a gap in the understanding of this modification. Here, we identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nsmb.2523) contains supplementary material, which is available to authorized users.


title: Formes graves d’infection par le virus A(H1N1)v2009 à La Réunion en 2009 et en 2010

text: In the Southern hemisphere, Réunion Island acts as a sentinel for infections preferentially occurring during the austral winter that are likely to reach the Northern hemisphere a few months later. We relate the main features concerning patients that were admitted during years 2009 and 2010 in our intensive care unit with an A(H1N1)v2009 infection, mainly for acute respiratory distress. Demographic, clinical, and biological data as well as given medications and outcome were prospectively collected among all PCR-confirmed influenza-infected patients. In 2009 and 2010, 25 patients met the criteria. Patients’ median age was 40.4 (±17.4) years. Most of them (22/25) had comorbidities such as: chronic diseases, overweight, obesity, pregnancy, and Down syndrome. Maximum bed-occupation rate was 10 days per million inhabitants. Main diagnosis for ICU admission was virus-related pneumonia. Twenty-two out of 25 patients needed mechanical ventilation, some required rescue therapies such as extracorporeal membranous oxygenation (ECMO) or hi-frequency oscillation ventilation (HFOV), both only available in few French hospitals. Within the study period, 12 patients died (48%) mainly of multi-organ failure. Through 2009 and 2010 autumn and winter periods, for several weeks, the A(H1N1)v2009 virus infection resulted in a significant increase of workload in Réunion Island ICUs. In 2010, the failure of the mass immunization campaign, particularly among the at-risk groups, led to severe cases of A(H1N1)v2009 infections, particularly among patients with comorbidities. Our data may contribute toward better management of influenza virus pandemics in the future.


Health biotechnology in China—reawakening of a giant


title: Preparing for the next Zika

text: Lessons from the US Biodefense program should inform international efforts to build a medical countermeasure enterprise for emerging infectious diseases.


title: Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond

text: In less than 20 years, the first selective type 5 phosphodiesterase inhibitor, sildenafil, has evolved from a potential anti-angina drug to an on-demand oral treatment for erectile dysfunction (Viagra), and more recently to a new orally active treatment for pulmonary hypertension (Revatio). Here we describe the key milestones in the development of sildenafil for these diverse medical conditions, discuss the advances in science and clinical medicine that have accompanied this journey and consider possible future indications for this versatile drug.


title: Antiviral agents active against influenza A viruses

text: The recent outbreaks of avian influenza A (H5N1) virus, its expanding geographic distribution and its ability to transfer to humans and cause severe infection have raised serious concerns about the measures available to control an avian or human pandemic of influenza A. In anticipation of such a pandemic, several preventive and therapeutic strategies have been proposed, including the stockpiling of antiviral drugs, in particular the neuraminidase inhibitors oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GlaxoSmithKline). This article reviews agents that have been shown to have activity against influenza A viruses and discusses their therapeutic potential, and also describes emerging strategies for targeting these viruses.


Research Letters


title: Patent protection and access to genetic resources

text: Developing countries and patent offices have shown differing approaches to patent specification disclosure requirements and benefit sharing.


title: Dealing with mass death in disasters and pandemics: Some key differences but many similarities

text: PURPOSE: There are many differences in how authorities handle the dead during mass death incidents involving disasters and pandemics. These differences would suggest that planning for a disaster death and planning for a pandemic death should be done separately. This may be true to some extent, however, there are many similarities between the two that this article will seeks to examine. The main objective of this study is to show that planning for both disasters and pandemics should either be done by a single entity that coordinates both types of responses, or by agencies that communicate closely and frequently. DESIGN/METHODOLOGY/APPROACH: This study compared mass death incidents predominantly within the Canadian historical record, including disasters and pandemics. It took a specific look at the influenza pandemic of 1918 in North America and how the dead were handled. FINDINGS: Both disasters and pandemics offer unique challenges in handling the dead and documenting the incident. In a pandemic the cause of death is usually clear, while in a disaster it is not always understood. However, the similarities they hold in common must not be overlooked. They will involve immense and complicated amounts of paperwork, cause a shortage of supplies (be it medical, food or otherwise) and create the need for assistance. ORIGINALITY/VALUE: The research finds that though disasters and pandemics are often handled differently by the various agencies involved, they should be treated alike and dealt with in the same manner.


title: Why pandemic response is unique: powerful experts and hands-off political leaders

text: PURPOSE: The purpose of this paper is to show that 2009 H1N1 “swine” influenza pandemic vaccination policies deviated from predictions established in the theory of political survival, and to propose that pandemic response deviated because it was ruled by bureaucratized experts rather than by elected politicians. DESIGN/METHODOLOGY/APPROACH: Focussing on the 2009 H1N1 pandemic, the paper employs descriptive statistical analysis of vaccination policies in nine western democracies. To probe the plausibility of the novel explanation, it uses quantitative and qualitative content analyses of media attention and coverage in two deviant cases, the USA and Denmark. FINDINGS: Theories linking political survival to disaster responses find little empirical support in the substantial cross-country variations of vaccination responses during the 2009 H1N1 pandemic. Rather than following a political logic, the case studies of media coverage in the USA and Denmark demonstrate that the response was bureaucratized in the public health agencies (CDC and DMHA, respectively). Hence, while natural disaster responses appear to follow a political logic, the response to pandemics appears to be more strongly instituted in the hands of bureaucratic experts. RESEARCH LIMITATIONS/IMPLICATIONS: There is an added value of encompassing bureaucratic dynamics in political theories of disaster response; bureaucratized expertise proved to constitute a strong plausible explanation of the 2009 pandemic vaccination response. PRACTICAL IMPLICATIONS: Pandemic preparedness and response depends critically on understanding the lessons of the 2009 H1N1 pandemic; a key lesson supported by this paper is that expert-based agencies rather than political leaders are the pivotal actors. ORIGINALITY/VALUE: This paper is the first to pinpoint the limitations of political survival theories of disaster responses with respect to the 2009 pandemic. Further, it is among the few to analyze the causes of variations in cross-country pandemic vaccination policies during the 2009 H1N1 pandemic.


title: The “wicked problems” of governing UK health security disaster prevention: The case of pandemic influenza

text: PURPOSE: The purpose of this paper is to examine the governance and policy-making challenges in the context of “wicked problems” based on the case of pandemic influenza. DESIGN/METHODOLOGY/APPROACH: The case study research is based on an analysis of official documentation and interviews with policy elites at multiple levels of UK governance. FINDINGS: Results of this study show that policy actors regard risk communication, the dynamics of international public policy and UK territorial governance as the main governance challenges in the management of influenza at a macro-level. The paper also serves to identify that although contingencies management for epidemiological issues require technical and scientific considerations to feature in governance arrangements, equally there are key “wicked problems” in the context public policy that pervade the health security sector. PRACTICAL IMPLICATIONS: The study indicates the need to build in resources at a national level to plan for policy coordination challenges in areas that might at first be seen as devoid of political machinations (such as technical areas of public policy that might be underpinned by epidemiological processes). The identification of the major governance challenges that emerge from the pandemic influenza case study is a springboard for a research agenda in relation to the analysis of the parallels and paradoxes of governance challenges for health security across EU member states. ORIGINALITY/VALUE: This paper provides a novel interrogation of the pandemic influenza case study in the context of UK governance and public policy by providing a strategic policy lens from perspective of elites.


title: RNA at Santa Cruz

text: Nestled in an atmosphere that resembles a national park, the Center for Molecular Biology of RNA at the University of California, Santa Cruz is fulfilling Harry Noller's vision of bringing together multidisciplinary researchers to solve problems that range from finding obscure RNAs to understanding the origin of life.


title: Targeting vesicle size

text: An amphipathic peptide has been engineered and is capable of penetrating the blood–brain barrier as well as possessing a potent antiviral activity against Zika and other mosquito-borne viruses.


title: Major advances against a moving target of CNS infections

text: CNS infections have severe manifestations, often leading to high mortality, but the CNS is usually not the primary target of pathogens, leaving a window of opportunity to prevent neuroinvasion. We must prioritize development of therapies to prevent neurological sequelae that cause long-lasting morbidity and disease burden on society.


title: Complement, a target for therapy in inflammatory and degenerative diseases

text: The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd4657) contains supplementary material, which is available to authorized users.


title: Child-Turcotte-Pugh Score, MELD Score and MELD-Na Score as Predictors of Short-Term Mortality among Patients with End-Stage Liver Disease in Northern India

text: BACKGROUND AND OBJECTIVES: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD) and MELD-sodium (MELD-Na) scores are used for predicting disease severity and mortality among patients with end-stage liver disease. However, data regarding their usefulness in predicting the short-term outcome of end-stage liver disease are not available in India. This prospective study compared the CTP score, MELD score and MELD-Na score as predictors of short-term outcome among patients with end-stage liver disease. METHODS: CTP, MELD and MELD-Na scores were determined in 171 patients with end-stage liver disease at a tertiary healthcare centre in India at the time of admission, and the concordance (C-) statistics of the three scores for 3-month mortality were assessed and compared. The aetiology of end-stage liver disease and the clinical presentation were determined. RESULTS: The CTP score, MELD score and MELD-Na score on day 1 were significantly higher among non-survivors than among survivors (p < 0.0001 each). The C-statistic for 3-month mortality for the CTP score was 0.93 (p < 0.0001), that for the MELD score was 0.86 (p < 0.0001) and that for the MELD-Na score was 0.83 (p < 0.0001). The C-statistics of these scores differed significantly for 3-month mortality, and the CTP score was better than the MELD (p < 0.0001) and MELD-Na (p < 0.0001) scores in predicting 3-month mortality. CONCLUSIONS: The CTP, MELD and MELD-Na scores were very good predictors of mortality at 3 months among patients with end-stage liver disease. The CTP score was superior to the MELD and MELD-Na scores in predicting 3-month mortality.


title: Genus Coltivirus (family Reoviridae): genomic and morphologic characterization of Old World and New World viruses

text: We report a genomic and morphologic study of the European Eyach (EYA) virus (genus Coltivirus, family Reoviridae) and a comparative analysis with the American Colorado tick fever (CTF) virus (the type species of the genus). The previously established, but distant, antigenic relationship between these viruses was strengthened by genetic findings (presence of cognate genes, amino acid identity between 55 and 88%, similar conserved terminal motifs, suspected read-through phenomenon in segment 9 of both viruses) and by indistinguishable ultramicroscopic morphologies. Moreover, putative constitutive modifying enzyme activities were suspected to be carried out by homologous viral proteins (RNA-dependent RNA polymerase, methyl/guanylyl transferase, NTPase). These findings, together with the comparative analysis to genomes of south-east Asian isolates, support the recent classification of arboviruses with 12 segments of dsRNA within two distinct genera (genus Coltivirus and genus Seadornavirus) and raise interesting questions about the evolutionary origins of coltiviruses. The previously proposed hypothesis that EYA virus was derived from an ancestral virus introduced in Europe with the migration of lagomorphs from North-America, would imply a divergence date between American and European isolates of over 50 million years ago (MYA). This analysis allows for the first time to propose an evolutionary rate for virus dsRNA genomes which was found to be in the order of 10(−8) to 10(−9) mutations/nt/year, a rate similar to that of dsDNA genomes.


title: Der Notfallplan des Krankenhauses: Grundlagen und allgemeine Struktur

text: A hospital emergency plan commonly consists of three main chapters dealing with the general aspects of emergency operation and the special aspects of external and internal emergencies. The extent of these chapters is restricted to general understanding and is completed by special instructions (emergency action plan, staff lists, material lists, situation plans) for each department. Due to its security significance, the emergency plan is handled confidential. External emergencies include mass casualty incidents, incidents with a large number of intoxicated patients, the care of patients with dangerous infectious diseases and NBC emergencies. Internal emergencies include fire and other environmental threats, the breakdown of the electrical power and water supply, the breakdown of the telephone system and other situations like bomb threat and taking of hostages. Any emergency call is sent to a special emergency phone, and a defined, experienced physician decides to activate the emergency plan. With the change from routine to emergency service, a chain of command is installed. The hospital staff deals with administrational and organizational aspects, whereas the medical staff is in charge of immediate patients' care. For each external emergency, the deployment of personnel and material and the basic organizational aspects are ordered. Comparable preparations are given for internal emergencies. To achieve realistic emergency planning, repeated evaluations and practical exercises are necessary. Furthermore, a basic independence of the hospital with respect to stocks, preparation and sterilization of instruments and catering is essential to ensure its function even under adverse conditions.


title: Der Notfallplan des Krankenhauses bei ABC-Gefahrenlagen

text: Hospital emergency department preparedness for mass-casualty incidents involving nuclear, biological or chemical (NBC) threats relies on close cooperation between hospital and pre-hospital emergency staff. It is essential that the hospital is immediately secured from unauthorized intrusion in order to avoid contamination of the hospital area and staff. The strategy of the pre-hospital emergency staff to avoid the unnecessary spread of contaminated material involves thorough decontamination of exposed persons near the site of the incident and coordinated transport to the primary care hospitals after decontamination. However, uncoordinated access of contaminated victims requires emergency decontamination by hospital staff. Thus, hospital staff must be prepared to provide in-hospital decontamination. Coordinated admission of contaminated patients into the NBC primary care hospital relies on a thorough decontamination by pre-hospital emergency staff at a decontamination site installed outside the hospital. Screening of patients is performed by hospital staff with special expertise in emergency medicine. Following admission, each patient is assigned to a team of specialists. Pre-hospital patient documentation is switched to inhospital documentation after admission using machine-readable electronic admission numbers.


Back to the roots: Stehen wir vor einem neuen Zeitalter der Infektionskrankheiten?


title: Patterns of Rift Valley fever virus seropositivity in domestic ruminants in central South Africa four years after a large outbreak

text: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis showing complex epidemiological patterns that are poorly understood in South Africa. Large outbreaks occur in the central interior at long, irregular intervals, most recently in 2010–2011; however, the level of herd immunity of ruminant livestock, a key determinant of outbreaks, is unknown. During 2015–2016 a cross-sectional study on 234 randomly-selected farms investigated the prevalence, patterns of, and factors associated with, antibodies to RVF virus (RVFV) in livestock in an area heavily affected by that outbreak. A RVFV inhibition ELISA was used to screen 977 cattle, 1,549 sheep and 523 goats and information on potential risk factors was collected using a comprehensive questionnaire. The estimated RVFV seroprevalence, adjusted for survey design, was 42.9% in cattle, 28.0% in sheep and 9.3% in goats, showing a high degree of farm-level clustering. Seroprevalence increased with age and was higher on private vs. communal land, on farms with seasonal pans (temporary, shallow wetlands) and perennial rivers and in recently vaccinated animals. Seropositivity amongst unvaccinated animals born after the last outbreak indicates likely viral circulation during the post-epidemic period. The current level of herd immunity in livestock may be insufficient to prevent another large outbreak, should suitable conditions recur.


Translational medicine in China I: Perspectives from Chinese physicians and scientists


title: Protective Effect of Dexmedetomidine on Acute Lung Injury via the Upregulation of Tumour Necrosis Factor-α-Induced Protein-8-like 2 in Septic Mice

text: The aim of the present study was to investigate whether TIPE2 participates in the protective actions of dexmedetomidine (DEX) in a mouse model of sepsis-induced acute lung injury (ALI). We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Control mice were infected with an adeno-associated virus expressing no transgene. Three weeks later, an animal model of caecal ligation-perforation (CLP)-induced sepsis was established. DEX was administered intravenously 30 min after CLP. Twenty-four hours after sepsis, lung injury was assayed by lung histology, the ratio of polymorphonuclear leukocytes (PMNs) to total cells in the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) activity, BALF protein content and the lung wet-to-dry (W/D) weight ratio. Proinflammatory factor levels in the BALF of mice were measured. The protein expression levels in lung tissues were analysed by Western blotting. The results showed that DEX treatment markedly mitigated sepsis-induced lung injury, which was characterized by the deterioration of histopathology, histologic scores, the W/D weight ratio and total protein levels in the BALF. Moreover, DEX markedly attenuated sepsis-induced lung inflammation, as evidenced by the decrease in the number of PMNs in the BALF, lung MPO activity and proinflammatory cytokines in the BALF. In addition, DEX dramatically prevented sepsis-induced pulmonary cell apoptosis in mice, as reflected by decreases in the number of TUNEL-positive cells, the protein expression of cleaved caspase-9 and cleaved caspase 3 and the Bax/Bcl-2 ratio. In addition, evaluation of protein expression showed that DEX blocked sepsis-activated JNK phosphorylation and NF-κB p65 nuclear translocation. Similar results were also observed in the TIPE2 overexpression group. Our study demonstrated that DEX inhibits acute inflammation and apoptosis in a murine model of sepsis-stimulated ALI via the upregulation of TIPE2 and the suppression of the activation of the NF-κB and JNK signalling pathways.


title: An analysis of sources of risk in the consumer electronics industry

text: The consumer electronics industry is a $240 billion global industry with a small number of highly competitive global players. We describe many of the risks associated with any global supply chain in this industry. As illustration, we also list steps that Samsung Electronics and its subsidiary, Samsung Electronics UK, have taken to mitigate these risks. Our description of the risks and illustration of mitigation efforts provides the backdrop to identify areas of future research.


title: Molecular Detection of Streptococcus pyogenes by Strand Invasion Based Amplification Assay

text: INTRODUCTION: Streptococcus pyogenes (group A Streptococcus, GAS) is responsible for a variety of highly communicable infections, accounting for 5–15 and 20–30% of sore throat hospital visits in adults and children, respectively. Prompt diagnosis of GAS can improve the quality of patient care and minimize the unnecessary use of antibiotics. OBJECTIVE: Our objective was to develop an alternative nucleic acid amplification method for the diagnosis of GAS. METHOD: We developed and evaluated a strand invasion based amplification (SIBA) assay to rapidly and specifically detect GAS. The performance of the developed GAS SIBA assay was compared with an established GAS polymerase chain reaction (PCR) assay. RESULTS: The GAS SIBA assay detected small amounts (ten copies) of S. pyogenes DNA within 13 min. The rapid detection time was achieved in part by optimization of magnesium concentration and reaction temperature. The sensitivity and specificity of the GAS SIBA assay for detection of S. pyogenes from clinical specimens were both 100%, and clinical specimens were detected within ~ 8 min of starting the reaction. CONCLUSION: Because the GAS SIBA assay is performed at low and constant temperature, it can be used both in centralized laboratories and for point-of-care testing. Furthermore, given its short detection time and strong analytical performance, the GAS SIBA assay could help to improve patient care and minimize unnecessary prescription of antibiotics.


title: Management of Influenza Virus Infections with Neuraminidase Inhibitors: Detection, Incidence, and Implications of Drug Resistance

text: Although influenza vaccination remains the primary method for the prevention of influenza, efficacy may be limited by a poor match between the vaccine and circulating strains and the poor response of elderly patients. Hence, there is an important role for antiviral therapy in the management of influenza. While amantadine and rimantadine have been available for the treatment of influenza in some countries for several years, they are only effective against influenza A viruses, they can have neurological and gastrointestinal adverse effects, and resistant virus is rapidly generated. Neuraminidase inhibitors, a new class of drug, are potent and specific inhibitors of all strains of influenza virus, and they have minimal adverse effects. The greatest benefit is seen in those patients presenting <30 hours after development of influenza symptoms, those with severe symptoms or those in high-risk groups. In addition to treatment of the infection, both drugs are effective prophylactically and have been shown to limit spread of infection in close communities, such as families and in nursing homes. No resistant virus strains have been isolated from normal individuals treated with zanamivir. Resistant virus can be isolated from approximately 1% of adults and 5% of paediatric patients with influenza treated with oseltamivir. However, infectivity of mutant viruses is generally compromised. Governments spend millions of dollars on influenza vaccination campaigns; however, once influenza virus is circulating in the community, vaccination cannot limit the spread of disease. A greater promotion of the use of neuraminidase inhibitors for the treatment and prevention of influenza could have a significant impact on limiting its spread. This could result in saving millions of dollars, not only in direct costs associated with medical and hospital care, but also significant savings in indirect costs associated with the loss of productivity at work, school and home environments. For the benefit of all communities, there needs to be a greater awareness of the symptoms of influenza and the efficacy of neuraminidase inhibitors in disease treatment.


title: Molecular Diagnostic Assays for Detection of Viral Respiratory Pathogens in Institutional Outbreaks

text: Outbreaks of viral respiratory disease in institutions may be associated with high morbidity and mortality, depending upon the viral etiology and the age and immune status of the affected patients. Control of outbreaks may include isolation and/or cohorting, and prohylaxis or treatment with specific antiviral agents may be indicated, all dependent upon the specific cause of the outbreak. Conventional methods of viral diagnosis detect only a limited number of the viruses that are known to cause outbreaks. The availability of sensitive and specific molecular assays has facilitated rapid diagnosis of a wider range of viruses from respiratory outbreaks. Molecular methods have distinct advantages over conventional methods, including the ability to rapidly develop assays for emerging viruses and new variants of existing viruses. In addition, molecular testing allows rapid detection of resistance to antiviral agents or mutations leading to increased virulence. However, high-throughput molecular testing requires batch processes that may compromise the ability to respond quickly to urgent testing demands.


title: SARS, pandemic influenza and Ebola: The disease control styles of Britain and the United States

text: Some researchers claim that nation states have begun to conform to an internationally uniform response to infectious disease. A potential barrier to this development are the distinct systems of disease control that industrialized nation states have developed over long periods of time. I explain the divergent public policy responses of the United Kingdom and the United States to SARS, pandemic influenza and Ebola by taking a historical approach. I examine the different medical theories of disease that existed in Britain and America in the nineteenth century as each country began to develop its public health system. I also examine where in the state apparatus disease control was located in each country. In Britain disease control was historically part of the welfare sector of the state, while in the United States it was originally operated by the military. These different starting conditions helped push Britain and the United States along different paths of disease control and this helps explain why they respond to contemporary diseases in such different ways. The ‘historical durability’ national styles of disease may make it more difficult for the international community to enact a truly uniform response to pandemics.


Blutdruckvariabilität zeigt kardiovaskuläres Risiko


title: ‘One medicine—one pathology’: are veterinary and human pathology prepared?

text: The American Medical Association and the American Veterinary Medical Association have recently approved resolutions supporting ‘One Medicine’ or ‘One Health’ that bridge the two professions. The concept is far from novel. Rudolf Virchow, the Father of Modern Pathology, and Sir William Osler, the Father of Modern Medicine, were outspoken advocates of the concept. The concept in its modern iteration was re-articulated in the 1984 edition of Calvin Schwabe's ‘Veterinary Medicine and Human Health.’ The veterinary and medical pathology professions are steeped in a rich history of ‘One Medicine,’ but they have paradoxically parted ways, leaving the discipline of pathology poorly positioned to contribute to contemporary science. The time has come for not only scientists but also all pathologists to recognize the value in comparative pathology, the consequences of ignoring the opportunity and, most importantly, the necessity of preparing future generations to meet the challenge inherent in the renewed momentum for ‘One Medicine.’ The impending glut of new genetically engineered mice creates an urgent need for prepared investigators and pathologists.


title: Microbial burden and diversity of commercial airline cabin air during short and long durations of travel

text: Total microbial burden and diversity associated with commercial airliner cabin air was assessed by molecular methods in 125 air samples from the business-class sections of 16 domestic and international flights. Viable microbial burden within these cabin air parcels constituted only 1–10% of the total microbial population and ranged from below detection limits to 1.2 × 10(4) cells m(–3) as determined with a validated ATP-based technology. Cultivable bacterial diversity was almost entirely limited to Gram-positive bacteria such as Staphylococcus and Bacillus. In contrast, cloning and sequencing 16S rRNA gene directly from the samples without cultivation indicated a significantly broader diversity, as sequences representing more than 100 species, and encompassing 12 classes of bacteria, were retrieved in varying abundance. Sequences of proteobacterial and Gram-positive lineage were retrieved most frequently (58% and 31% of all clone sequences, respectively), with Gram-positive and α-proteobacterial sequences dominating international flight samples and β- and γ-proteobacterial sequences comprising the largest portion of those retrieved from domestic flights. Significant differences in bacterial load and diversity were noted between samples obtained on domestic and international flights. The disparities observed in microbial abundance and diversity further underscore the immense value of state-of-the art molecular assays in augmenting traditional culture-based techniques. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ismej.2008.11) contains supplementary material, which is available to authorized users.


title: Commentary: How useful is ‘burden of disease’ to set public health priorities for infectious diseases?

text: For many infectious diseases, a low burden of disease does not equate to reduced potential public health importance. Many zoonotic infectious diseases have the potential for human-to-human transmission with potentially devastating consequences as currently seen with Ebola. Policymakers should not be lulled into thinking that the best use of resources is to allocate them only to the most obvious current problems.


title: The impact of hand, foot and mouth disease control policies in Singapore: A qualitative analysis of public perceptions

text: Hand foot and mouth disease (HFMD) is a widespread pediatric disease in Asia. Most cases are relatively mild and caused by Coxsackie viruses, but in epidemics caused by Enterovirus 71, severe complications can occur. In response to the deaths of dozens of children in a 1997 outbreak (Podin in BMC Public Health 6:180,1 Abubakar in Virus Res 61(1):1–9,2 WHO in3), Singapore practices childcare centre surveillance, case-isolation, and short-term closure of centres. We conducted 44 in-depth interviews with teachers, principals, and parents at four childcare centres in Singapore to better understand experiences with current control policies. We used applied thematic analysis to identify recurrent and unique themes. Participants were conflicted by perceiving HFMD as a severe illness and reported a sense of helplessness when hygiene and social-isolation efforts failed. They perceived that severity of HFMD influenced Singapore’s choice of existing policies despite a lack of evidence of their effectiveness. Documenting stakeholders’ perspectives clarifies the impact of control measures and how to communicate policy changes.


Contagious Narratives: Towards a Global Epidemiology in Priscilla Wald's Contagious


title: Rationality, Risk and Response: A Research Agenda for Biosecurity

text: This article considers how threats become constituted as problems requiring policy responses, and how one might account for such problematizations and responses. Focusing specifically on the threat from bioterrorism, it draws on a broadly constructivist approach to risk, and highlights how ideas around political rationalities, styles of thought, forms of risk and frameworks of knowledge can be useful in thinking about emerging biosecurity policies. It suggests that a comparative study of Britain and the United States might help to clarify how the threat of bioterrorism is being constructed by various groups, how support for particular ‘framings’ of the threat is being mobilized and taken up in policy networks, and how this is linked to different courses of action in response to the possibility of bioterrorism.


title: A 2009 cross-sectional survey of procedures for post-mortem management of highly infectious disease patients in 48 isolation facilities in 16 countries: data from EuroNHID

text: PURPOSE: The handling of human remains may pose a risk for transmission of highly infectious agents. The use of appropriate biosafety measures is very important in case of management of patients deceased from highly infectious diseases (HIDs), such as Ebola virus disease. This paper presents the capabilities and resources in this field in 16 European countries, and suggests indications for the safe post-mortem management of HID patients. METHODS: The European Network for Highly Infectious Diseases conducted in 2009 a survey in 48 isolation facilities in 16 European countries. A set of standardized checklists, filled during on-site visits, have been used for data collection. RESULTS: Thirty-nine facilities (81.2 %) reported to have written procedures for the management of human remains, and 27 (56.2 %) for the performance of autopsies in HID patients. A Biosafety Level 3 autopsy room was available in eight (16.6 %) facilities, other technical devices for safe autopsies were available in nine (18.7 %). Overall, four facilities (8.3 %) reported to have all features explored for the safe management of human remains. Conversely, in five (10.4 %) none of these features were available. CONCLUSIONS: The level of preparedness of surveyed isolation facilities in the field of post-mortem management in case of HIDs was not satisfactory, and improvements are needed.


Autopsy


title: Regulating Hybrids: ‘Making a Mess’ and ‘Cleaning Up’ in Tissue Engineering and Transpecies Transplantation

text: This paper explores the institutional regulation of novel biosciences, hybrid technologies that often disturb and challenge existing regulatory frameworks. Developing a conceptual vocabulary for understanding the relationship between material and institutional hybrids, the paper compares human tissue engineering (TE) and xenotransplantation (XT), areas of innovation which regulators have sought to govern separately and in isolation from one another. Contrasting definitional boundaries and regulatory mechanisms partition them socio-institutionally. But despite these attempts at purification, TE and XT have proven increasingly difficult to tell apart in practical and material terms. Human and animal matters, cell cultures and tissue products have much greater corporeal connection than has been institutionally recognized, and are therefore a source of acute instability in the regulation of implants and transplants. This paper tells the story of how the messy worlds of TE and XT have leaked into one another, calling into question the abilities of regulation to adequately control hybrid innovations.


Working on the social determinants of health is central to public health


title: Exploiting the Therapeutic Potential of MicroRNAs in Viral Diseases: Expectations and Limitations

text: New therapeutic approaches are urgently needed for serious diseases, including cancer, cardiovascular diseases, viral infections, and others. A recent direction in drug development is the utilization of nucleic acidbased therapeutic molecules, such as antisense oligonucleotides, ribozymes, short interfering RNA (siRNA), and microRNA (miRNA). miRNAs are endogenous, short, non-coding RNA molecules. Some viruses encode their own miRNAs, which play pivotal roles in viral replication and immune evasion strategies. Conversely, viruses that do not encode miRNAs may manipulate host cell miRNAs for the benefits of their replication. miRNAs have therefore become attractive tools for the study of viral pathogenesis. Lately, novel therapeutic strategies based on miRNA technology for the treatment of viral diseases have been progressing rapidly. Although this new generation of molecular therapy is promising, there are still several challenges to face, such as targeting delivery to specific tissues, avoiding off-target effects of miRNAs, reducing the toxicity of the drugs, and overcoming mutations and drug resistance. In this article, we review the current knowledge of the role and therapeutic potential of miRNAs in viral diseases, and discuss the limitations of these therapies, as well as strategies to overcome them to provide safe and effective clinical applications of these new therapeutics.