title: The Importance of Understanding the Human–Animal Interface: From Early Hominins to Global Citizens

text: The complex relationships between the human and animal species have never ceased to evolve since the emergence of the human species and have resulted in a human–animal interface that has promoted the cross-species transmission, emergence and eventual evolution of a plethora of infectious pathogens. Remarkably, most of the characteristics of the human–animal interface—as we know it today—have been established long before the end of our species pre-historical development took place, to be relentlessly shaped throughout the history of our species. More recently, changes affecting the modern human population worldwide as well as their dramatic impact on the global environment have taken domestication, agriculture, urbanization, industrialization, and colonization to unprecedented levels. This has created a unique global multi-faceted human–animal interface, associated with a major epidemiological transition that is accompanied by an unexpected rise of new and emerging infectious diseases. Importantly, these developments are largely paralleled by medical, technological, and scientific progress, continuously spurred by our never-ending combat against pathogens. The human–animal interface has most likely contributed significantly to the evolutionary shaping and historical development of our species. Investment in a better understanding of this human–animal interface will offer humankind a future head-start in the never-ending battle against infectious diseases.


title: Risques d’importation des maladies infectieuses exotiques en France métropolitaine : détection, alerte et réponse

text: SUMMARY The French public health institute is responsible for promoting and coordinating threats the detection and assessment of health risks, and for suggesting possible responses. Transmissible diseases affecting both human and animal health are the focus of surveillance networks. Early detection of potential infectious threats is based on the screening of “ alert signals “ identified through routine surveillance networks and other systems. The quality and accuracy of these signals is first verified, before assessing, through a multidisciplinary approach, the risk of introduction and dissemination. This article examines specific cases illustrating the process of detection, risk analysis and response, with respect to infectious threats that are endemic in tropical regions and have the potential to be imported into metropolitan France. For both novel pathogens and exotic diseases — which, not being endemic in France, are less well known — the analysis and response process must regularly be adapted to the latest epidemiological, clinical and biological findings, taking interactions between the pathogen, host, and environment into consideration. The need to improve reaction times and risk assessment is also discussed.


title: Covido‐pedago‐phobia

text: Breathlessness, aches and pains, abdominal discomfort and hoarse voice! These may sound like the clinical presentation of COVID‐19, but Nay! These are the symptoms experienced by the countless health professions education (HPE) teachers who have suddenly been thrust into the online world to engage learners.


title: SARS-CoV-2 Detection in Different Respiratory Sites: A Systematic Review and Meta-Analysis

text: Background: The accurate detection of SARS-CoV-2 through respiratory sampling is critical for the prevention of further transmission and the timely initiation of treatment for COVID-19. There is a diverse range of SARS-CoV-2 detection rates in reported studies, with uncertainty as to the optimal sampling strategy for COVID-19 diagnosis and monitoring. Methods: We performed a systematic review and meta-analysis of studies comparing respiratory sampling strategies for the detection of SARS-CoV-2 RNA. The inclusion criteria were studies that assessed at least two respiratory sampling sites (oropharyngeal swab, nasopharyngeal swab, and sputum) in participants with COVID-19. The percentage positive tests were compared between sampling modalities by constructing a Z-test assuming independence and using the standard errors obtained from the random effects meta-analysis. Findings: From 1039 total studies, we identified 11 studies that met our inclusion criteria, with SARS-CoV-2 testing results from a total of 3442 respiratory tract specimens. Compared to nasopharyngeal swab sampling, sputum testing resulted in significantly higher rates of SARS-CoV-2 RNA detection while oropharyngeal swab testing had lower rates of viral RNA detection. Earlier sampling after symptom onset was associated with improved detection rates, but the differences in SARS-CoV-2 RNA detection by sampling method was consistent regardless of the duration of symptoms. Interpretation: The results support sputum sampling as a primary method of COVID-19 diagnosis and monitoring, and highlight the importance of early testing after symptom onset to increase the rates of COVID-19 diagnosis.


title: Current Status of Cell-Based Therapies for Respiratory Virus Infections: Applicability to COVID-19

text: Severe respiratory consequences of the COVID-19 pandemic have prompted urgent need for novel therapies. Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with the acute respiratory distress syndrome (ARDS), although not as yet well studied in respiratory virus-induced ARDS. Limited pre-clinical data suggest that systemic MSC administration can significantly reduce respiratory virus (Influenza strains H5N1 and H9N2)-induced lung injury, however, there are no available data in models of coronavirus respiratory infection. There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. These utilise a range of different cell sources, doses, dosing strategies, and targeted patient populations. To provide a rationale strategy to maximise potential therapeutic use, it is critically important to understand the relevant pre-clinical studies and postulated mechanisms of MSC actions in respiratory virus-induced lung injuries. These are presented along with consideration of current clinical investigations.


title: The next protein transition

text: Abstract Background Meeting the UN Sustainable Development Goals requires a relatively rapid transition towards a circular economy. Therefore, a multidisciplinary perspective is required to sketch why a transition from diets based primarily on animal proteins towards diets based primarily on plant proteins products is extremely urgent for both food security and sustainability. Scope and approach This review starts out by identifying ecological, economic and social aspects of sustainable food consumption. Subsequently, it is argued how protein supply is underlying and linking the top-3 of anthropogenic impacts based on the planetary boundaries concept, i.e. 1) biodiversity loss, 2) nitrogen cycle acceleration, and 3) carbon cycle acceleration (resulting in climate change). These environmental impacts associated with current Western food consumption need to be reduced urgently. In order to address the inefficiencies inherent to current dietary patterns, therefore, a ranked list of more sustainable options is proposed, based on their order of magnitude. Addressing consumers, industry, and governmental stakeholders plus cultural aspects, challenges and options are sketched. Key findings and conclusions Clearly, a dietary transition from primarily animal towards plant protein products is required. Fortunately, new dietary guidelines are increasingly taking sustainability into account and the contours of a diet transition are slowly emerging.


title: Chapter 29 Design of Genomic Signatures for Pathogen Identification and Characterization

text: Publisher Summary This chapter addresses issues associated with the identification of signatures based on genomic DNA/RNA, which can be used to identify and characterize pathogens for biodefense and microbial forensic goals. Genomic signature-based identification techniques have the advantage of being precise, highly sensitive, and relatively fast in comparison to biochemical typing methods and protein signatures. Classic biochemical typing methods were developed long before knowledge of DNA and resulted in dozens of tests that are used to roughly characterize the major known pathogens. Genomic signatures can be intended for many different purposes and applied at multiple different resolutions. Organism signatures are intended to uniquely identify the organisms involved. Mechanism signatures can be best thought of as identifying particular genes that result in functional properties such as virulence, antibiotic resistance, or host range. The primary reason to identify mechanisms, independent of organisms, is to detect potential genetic engineering. A secondary reason is that nature has shared many important mechanisms on its own over the millennia, and thus they may not be sufficiently unique to identify specific organisms. Method signatures present yet another dimension of analyzing pathogens: evidence of potential bacterial genetic engineering may be seen in a genome by checking for traces of the bacterial vectors that may have been used to insert one or more foreign genes and related components into the genome being modified.


title: Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure

text: Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.


title: Chapter 11 Response at the State and Local Level

text: Abstract Chapter 11 covers the convergence of agencies from all levels of government to the scene of a biological event. In fact, many agencies from the federal level will respond to a chemical, biological, radiological/nuclear, and explosive incident, providing necessary resources. Planners within local jurisdictions need to maintain a list of the agencies, the contact numbers, and the resources available from each. State and local governments must be fully compliant with the National Incident Management System, which includes the adaptation of the Incident Command System. Unified or area command is an essential element in domestic incident management in which multiple jurisdictions and agencies are involved. It provides guidelines to enable agencies with different legal, geographic, and functional responsibilities to effectively coordinate, plan, and interact. Unified or area command removes much of the inefficiency and duplication of effort that can occur when agencies from different functional and geographic jurisdictions or agencies at different levels of government operate without a common system or organizational framework.


COVID-19 outbreak in France: Setup and activities of a mobile Extra Corporeal Membrane Oxygenation (ECMO) team during the first 3 weeks


title: Clinical Decision Support Tool and Rapid Point-of-Care Platform for Determining Disease Severity in Patients with COVID-19

text: SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40–83) and 9 (6–17), respectively, and area under the curve of 0.94 (95% CI 0.89–0.99). These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.


title: Activation of pro- and anti-inflammatory responses in lung tissue injury during the acute phase of PRRSV-1 infection with the virulent strain Lena

text: Porcine reproductive and respiratory syndrome virus (PRRSV) plays a key role in porcine respiratory disease complex modulating the host immune response and favouring secondary bacterial infections. Pulmonary alveolar macrophages (PAMs) are the main cells supporting PRRSV replication, with CD163 as the essential receptor for viral infection. Although interstitial pneumonia is by far the representative lung lesion, suppurative bronchopneumonia is described for PRRSV virulent strains. This research explores the role of several immune markers potentially involved in the regulation of the inflammatory response and sensitisation of lung to secondary bacterial infections by PRRSV-1 strains of different virulence. Conventional pigs were intranasally inoculated with the virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain and euthanised at 1, 3, 6 and 8 dpi. Lena-infected pigs exhibited more severe clinical signs, macroscopic lung score and viraemia associated with an increase of IL-6 and IFN-γ in sera compared to 3249-infected pigs. Extensive areas of lung consolidation corresponding with suppurative bronchopneumonia were observed in Lena-infected pigs. Lung viral load and PRRSV-N-protein(+) cells were always higher in Lena-infected animals. PRRSV-N-protein(+) cells were linked to a marked drop of CD163(+) macrophages. The number of CD14(+) and iNOS(+) cells gradually increased along PRRSV-1 infection, being more evident in Lena-infected pigs. The frequency of CD200R1(+) and FoxP3(+) cells peaked late in both PRRSV-1 strains, with a strong correlation between CD200R1(+) cells and lung injury in Lena-infected pigs. These results highlight the role of molecules involved in the earlier and higher extent of lung lesions in piglets infected with the virulent Lena strain, pointing out the activation of routes potentially involved in the restraint of the local inflammatory response.


title: Chapter 48 Mucosal Vaccine Development for Veterinary and Aquatic Diseases

text: Abstract Because most pathogens and food antigens enter the host via the mucosal surfaces, effective mucosal immunity is critical for maintaining homeostasis through immune regulation, tolerance, and induction of effective immune responses when needed. Thus the mucosa-associated lymphoid tissues represent an important target for vaccination. Indeed, more than 20 years of research have clearly demonstrated the benefits of mucosal vaccination versus systemic vaccination. Such benefits include local induction of secretory immunoglobulin A (SIgA) as well as activation and maturation of mucosal dendritic cells, homing of effector cells to the mucosal surfaces, expression of specific host defense peptides, and other innate effector molecules. In addition, mucosal vaccination offers the opportunity to induce colostral and lactogenic immunity during pregnancy and the possibility of avoiding neutralization of early life vaccines by maternal antibodies, both of which are critical for protecting the most susceptible from infectious diseases. Moreover, mucosal administration offers the advantage of inducing both effective systemic immunity and mucosal immunity, enhancing vaccine efficacy and providing improved protection. A number of animal vaccines are already administered via the mucosal surfaces, with many more to come over the next few years. It is gratifying to see that veterinary vaccine development has yet again taken a leadership role in exploring innovative approaches and technologies to mucosal vaccination. For the veterinary field, considerations for mucosal vaccine development and use necessarily include costs (often pennies per dose), mass delivery that preferably avoids animal restraint, and economic and trade considerations. In this chapter, we provide an overview of some of the existing vaccine technologies and discuss their advantages and disadvantages.


title: The Views of Medical Faculty Students in Turkey Concerning the COVID-19 Pandemic

text: The aim of this study was to elicit the views of medical faculty students regarding the COVID-19 pandemic. This descriptive study was performed with Ondokuz Mayıs University Medical Faculty students on 24–27 March, 2020. The Medical Faculty currently has 2051 students. A questionnaire was used as a data collection tool. For that purpose, the authors designed a questionnaire specifically for this research via the “Google Forms” web. This consisted of 40 open- and close-ended questions. The questionnaire was completed by 1375 (67.1%) students. Accordingly, 52.4% of medical students reported feeling mentally unwell. Although 50.8% of medical students reported generally/usually obtaining information about COVID-19 through the social media, 82.0% did not trust information/messages arriving through the social media and WhatsApp. We found that 86.7% of students regarded frequent hand washing as the most important means of protection against COVID-19, and 19.3% of students did not regard the COVID-19 pandemic as a severe public health problem for Turkey at that moment. In addition, 61.6% of students stated that a suppression strategy involving tight restrictions need to be applied to being the pandemic under control in Turkey. Use can be made of medical students in the transmission of accurate information during the COVID-19 pandemic. Students can be excellent activists on these subjects in countries in which medical education is suspended. Measures therefore need to be taken concerning the transmission of up to date and accurate information to medical students.


title: Human milk oligosaccharides: Shaping the infant gut microbiota and supporting health

text: Human milk oligosaccharides (HMO) are complex sugars which are found in breast milk at significant concentrations and with unique structural diversity. These sugars are the fourth most abundant component of human milk after water, lipids, and lactose and yet provide no direct nutritional value to the infant. Recent research has highlighted that HMOs have various functional roles to play in infant development. These sugars act as prebiotics by promoting growth of beneficial intestinal bacteria thereby generating short-chain fatty acids which are critical for gut health. HMOs also directly modulate host-epithelial immune responses and can selectively reduce binding of pathogenic bacteria and viruses to the gut epithelium preventing the emergence of a disease. This review covers current knowledge related to the functional biology of HMOs and their associated impact on infant gut health.


Le silence des questions sur la mort des aînés liée au Covid19


title: Is investing in religious institutions a viable pathway to reduce mortality in the population?

text: There is established and consistent findings from epidemiologic studies, among individuals, that religion— broadly assessed through frequency of attending worship services—is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.


Ethical Criteria for the Admission and Management of Patients in the ICU Under Conditions of Limited Medical Resources: A Shared International Proposal in View of the COVID-19 Pandemic


title: Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo

text: Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region.


title: Viral tricks to grid-lock the type I interferon system

text: Type I interferons (IFN) play a critical role in the innate immune avant-garde against viral infections. Virtually all viruses have developed means to counteract the induction, signaling or antiviral actions of the IFN circuit. Over 170 different virus-encoded IFN-antagonists from 93 distinct viruses have been described up to now, indicating that most viruses interfere with multiple stages of the IFN response. Although every viral IFN antagonist is unique in its own right, four main mechanisms are employed to circumvent innate immune responses: i) general inhibition of cellular gene expression, and ii) sequestration, iii) proteolytic cleavage or iv) proteasomal degradation of key components of the IFN system. The increasing understanding of how different viral IFN antagonists function has been translated to the generation of viruses with mutant IFN antagonists as potential live vaccine candidates. Moreover, IFN antagonists are attractive targets for inhibition by small-molecule compounds.


title: Infections virales émergentes

text: SUMMARY Emerging and re-emerging infectious diseases have again entered the public arena in recent years. This is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. Numerous pathogens, including viruses like West Nile, Chikungunya and Japanese encephalitis on the one hand, and hemorrhagic fever viruses like Ebola and Maburg, are particular concerns. Recently, the Corona virus responsible for SARS, which caused an epidemic sufficiently worrisome to challenge crisis management concepts, was successfully isolated. It is in this context that so-called “ bird flu’ “ , may be on the verge of causing a human pandemic. Pox and Monkeypox are “ virtually emerging “ viruses that have potential for use in bioterrorism. The management and treatment of these emerging infectious diseases calls for new approaches, organizations and infrastructures.


Akute Bronchitis und Influenza


title: Electroencephalogram (EEG) in COVID-19: a systematic retrospective study

text: Abstract Objectives: Although rare, neurological manifestations in SARS-CoV-2 infection are increasingly being reported. We conducted a retrospective systematic study to describe the electroencephalography (EEG) characteristics in this disease, looking for specific patterns. Methods: EEGs performed in patients with positive PCR for SARS-CoV-2 between 25/03/2020 and 06/05/2020 in the University Hospital of Bicêtre were independently reviewed by two experienced neurologists. We used the American Clinical Neurophysiology Society's terminology for the description of abnormal patterns. EEGs were classified into five categories, from normal to critically altered. Interobserver reliability was calculated using Cohen's kappa coefficient. Medical records were reviewed to extract demographics, clinical, imaging and biological data. Results: Forty EEGs were reviewed in 36 COVID-19 patients, 18 in intensive care units (ICU) and 22 in medicine units. The main indications were confusion or fluctuating alertness for 23 (57.5%) and delayed awakening after stopping sedation in ICU in six (15%). EEGs were normal to mildly altered in 23 (57.5%) contrary to the 42.5% where EEG alterations were moderate in four (10%), severe in eight (20 %) and critical in five (12.5%). Generalized periodic discharges (GPDs), multifocal periodic discharges (MPDs) or rhythmic delta activity (RDA) were found in 13 recordings (32.5%). EEG alterations were not stereotyped or specific. They could be related to an underlying morbid status, except for three ICU patients with unexplained encephalopathic features. Conclusion: In this first systematic analysis of COVID-19 patients who underwent EEG, over half of them presented a normal recording pattern. EEG alterations were not different from those encountered in other pathological conditions.


title: Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

text: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6–30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents in vitro and in vivo, with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10(6) copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in in vitro assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2′-fluoro-2′-deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy in vitro and in vivo, retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.


title: Detection and complete genome characterization of human enterovirus 118 from children with acute respiratory disease in China

text: Enterovirus 118 (EV-118) within species HEV-C was detected in two 5-month-old boys with pneumonia in China. The EV-118 from both cases was genetically closer to ISR10 strain from Israel than to PER161 strain from Peru based on VP1 gene sequences. The complete genome of the detected EV-118 consists of 7,360 nucleotides, excluding the poly (A) tail. The 5′UTR contains 669 nucleotides, and 3′UTR consists of 73 nucleotides. A single open reading frame from base 670 to 7,287 that encodes a 2,206-amino-acid polyprotein was featured. The base composition of the full genome is 27.9 % A, 24.2 % C, 24.4 % G, and 23.6 % U. Phylogenetic analysis of the full genome sequences illustrated EV-118 was genetically closer to EV-109 and EV-105, and the Chinese strain differed from Peru strain. In summary, the presence of EV-118 was confirmed in pediatric pneumonia cases and complete genome sequences were identified for the first time in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-014-1044-1) contains supplementary material, which is available to authorized users.


title: Molecular anatomy of subcellular localization of HSV-1 tegument protein US11 in living cells

text: Abstract The herpes simplex virus type I (HSV-1) US11 protein is an RNA-binding multifunctional regulator that specifically and stably associates with nucleoli. Although the C-terminal part of US11 was responsible for its nucleolar localization, the precise nucleolar localization signal (NoLS) and nuclear export signal (NES) of US11 and its nuclear import and export mechanisms are still elusive. In this study, fluorescence microscopy was employed to investigate the subcellular localization of US11 and characterize its transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein (EYFP), three novel NoLSs of US11 were for the first time mapped to amino acids 84–125, 126–152, and 89–146, respectively. Additionally, the NES was identified to locate between amino acids 89 and 119. Furthermore, the US11 protein was demonstrated to target to the cytoplasm through the NES by chromosomal region maintenance 1 (CRM1)-independent pathway, and to the nucleolus through Ran and importin β-dependent mechanism that does not require importin α5.


title: Engineering a Live Attenuated Porcine Epidemic Diarrhea Virus Vaccine Candidate via Inactivation of the Viral 2'-O-Methyltransferase and the Endocytosis Signal of the Spike Protein

text: Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets; however, effective and safe vaccines are still not available. We hypothesized that inactivation of the 2′-O-methyltransferase (2′-O-MTase) activity of nsp16 and the endocytosis signal of the spike protein attenuates PEDV yet retains its immunogenicity in pigs. We generated a recombinant PEDV, KDKE(4A), with quadruple alanine substitutions in the catalytic tetrad of the 2′-O-MTase using a virulent infectious cDNA clone, icPC22A, as the backbone. Next, we constructed another mutant, KDKE(4A)-SYA, by abolishing the endocytosis signal of the spike protein of KDKE(4A). Compared with icPC22A, the KDKE(4A) and KDKE(4A)-SYA mutants replicated less efficiently in vitro but induced stronger type I and type III interferon responses. The pathogenesis and immunogenicities of the mutants were evaluated in gnotobiotic piglets. The virulence of KDKE(4A)-SYA and KDKE(4A) was significantly reduced compared with that of icPC22A. Mortality rates were 100%, 17%, and 0% in the icPC22A-, KDKE(4A)-, and KDKE(4A)-SYA-inoculated groups, respectively. At 21 days postinoculation (dpi), all surviving pigs were challenged orally with a high dose of icPC22A. The KDKE(4A)-SYA- and KDKE(4A)-inoculated pigs were protected from the challenge, because no KDKE(4A)-SYA- and one KDKE(4A)-inoculated pig developed diarrhea whereas all the pigs in the mock-inoculated group had severe diarrhea, and 33% of them died. Furthermore, we serially passaged the KDKE(4A)-SYA mutant in pigs three times and did not find any reversion of the introduced mutations. The data suggest that KDKE(4A)-SYA may be a PEDV vaccine candidate. IMPORTANCE PEDV is the most economically important porcine enteric viral pathogen and has caused immense economic losses in the pork industries in many countries. Effective and safe vaccines are desperately required but still not available. 2′-O-MTase (nsp16) is highly conserved among coronaviruses (CoVs), and the inactivation of nsp16 in live attenuated vaccines has been attempted for several betacoronaviruses. We show that inactivation of both 2′-O-MTase and the endocytosis signal of the spike protein is an approach to designing a promising live attenuated vaccine for PEDV. The in vivo passaging data also validated the stability of the KDKE(4A)-SYA mutant. KDKE(4A)-SYA warrants further evaluation in sows and their piglets and may be used as a platform for further optimization. Our findings further confirmed that nsp16 can be a universal target for CoV vaccine development and will aid in the development of vaccines against other emerging CoVs.


title: Comments on "Cross‐species transmission of the newly identified coronavirus 2019‐nCoV"

text: After reading the article speculating that novel coronavirus from Wuhan may be transmitted to humans through snakes, I think the most critical analysis method is synonymous codon usage analysis, which estimated the relative synonymous codon usage (RSCU) of the 2019‐nCoV and its potential hosts. This article is protected by copyright. All rights reserved.


title: Evidence of infectivity of airborne porcine epidemic diarrhea virus and detection of airborne viral RNA at long distances from infected herds

text: Porcine epidemic diarrhea virus (PEDV) spread rapidly after being diagnosed in the USA in April 2013. In this study we assessed whether PEDV could become airborne and if so, whether the virus was infectious. Air samples were collected both from a room containing experimentally infected pigs and at various distances from the outside of swine farms experiencing acute PEDV outbreaks. Results indicated presence of infectious PEDV in the air from experimentally infected pigs and genetic material of PEDV was detected up to 10 miles downwind from naturally infected farms. Airborne transmission should be considered as a potential route for PEDV dissemination.


title: Multiple Presentations of LRBA Deficiency: a Single-Center Experience

text: INTRODUCTION: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency categorized as common variable immunodeficiency associated with autoimmune manifestations and inflammatory bowel diseases; however, the clinical spectrum has been extended. Here, we present our cohort of Turkish LRBA-deficient patients from a single center, demonstrating a diversity of clinical manifestations. METHOD: Seven affected individuals from five families were assessed retrospectively in this study. RESULTS: Of the seven patients with LRBA deficiency, four had homozygous, and two had compound heterozygous mutations. One patient remained disease free until the last follow-up (age 17 years). The most common clinical manifestations of the six symptomatic patients were organomegaly (6/6), autoimmunity (6/6), and chronic diarrhea (5/6). Recurrent infectious episodes were observed in three patients. None of the patients had hypogammaglobulinemia at presentation. B cell subpopulation analysis revealed low numbers of switched-memory B cell numbers in two of the four tested patients. During the disease course, three of the patients died, two of them underwent successful hematopoietic stem cell transplantation (HSCT) from matched sibling donors, and one is under abatacept therapy. CONCLUSION: LRBA defects should always be kept in mind as a differential diagnosis for patients with autoimmune disease affecting multiple organs, chronic diarrhea, and organomegalies. In our experience, early HSCT is a life-saving therapeutic strategy.


title: Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights

text: Abstract Rheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA.


title: A weapon the world needs

text: Both bottom-up and top-down planning is needed to prevent a global economic disaster. Michael T. Osterholm calls for action at all levels.


title: Rapid Viral Diagnosis of Orthopoxviruses by Electron Microscopy: Optional or a Must?

text: Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT). The simple negative staining technique of DEM was applied widely to smallpox diagnosis until the world-wide eradication of the human-specific pathogen in 1980. Since then, the threat of smallpox re-emerging through laboratory escape, molecular manipulation, synthetic biology or bioterrorism has not totally disappeared and would be a major problem in an unvaccinated population. Other animal poxviruses may also emerge as human pathogens. With its rapid results (only a few minutes after arrival of the specimen), no requirement for specific reagents and its “open view”, DEM remains an important component of virus diagnosis, particularly because it can easily and reliably distinguish smallpox virus or any other member of the orthopoxvirus (OPV) genus from parapoxviruses (PPV) and the far more common and less serious herpesviruses (herpes simplex and varicella zoster). Preparation, enrichment, examination, internal standards and suitable organisations are discussed to make clear its continuing value as a diagnostic technique.


title: Domestic Pig Unlikely Reservoir for MERS-CoV

text: We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature.


An outbreak of cutaneous anthrax in Yunnan, China


title: Beyond interferon

text: Interferon (IFN)-α has reigned supreme for decades as biotech's blockbuster antiviral. That looks set to change with a raft of antibody and nucleic acid therapies progressing through the pipeline.


title: Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

text: PURPOSE: Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal immunization. METHODS: TMC was synthesized by free radical polymerization and blank nanoparticles were prepared by ionic crosslinking of TMC and sodium tripolyphosphate. The model antigen (ovalbumin) was conjugated on the surface of blank nanoparticles (OVA-NP) through thioester bond formation. The cellular uptake of OVA-NP was investigated in Raw 264.7 macrophages and biodistribution of antigens was studied by the radioiodine labeling method. The immunological effects were evaluated by nasal administration of OVA-NP to Balb/C mice. The transport mechanism and nasal toxicity of OVA-NP were studied in rats. RESULTS: The cellular uptake of OVA-NP was significantly higher than that of ovalbumin-encapsulated nanoparticles (NPe) after 30 min. Nasally administered OVA-NP showed higher transport of antigens to cervical lymph nodes with higher targeting efficiency than all other groups. Compared with NPe, OVA-NP induced much higher levels of systemic and mucosal immune responses in Balb/C mice after three nasal immunizations. Ex vivo culturing of nasopharynx-associated lymphoid tissue (NALT) confirmed its participation in nasal immunization. The transport mechanism study revealed that OVA-NP can be transported across the nasal epithelium through glands and may be taken up in NALT through M cells. OVA-NP did not induce obvious toxicity to nasal mucosa or hemolysis in animals. CONCLUSION: The present study demonstrated that the conjugation of TMC nanoparticles with antigens is an effective strategy for nasal vaccination.


The COVID‐19 Airway Management Isolation Chamber (CAMIC) for Ears


title: Rapid and sensitive detection of canine distemper virus by one-tube reverse transcription-insulated isothermal polymerase chain reaction

text: BACKGROUND: Canine distemper virus (CDV) has been associated with outbreaks of canine infectious respiratory disease in shelters and boarding kennel environments. POCKIT(TM) Nucleic Acid Analyzer is a field-deployable device capable of generating automatically interpreted insulated isothermal polymerase chain reaction (iiPCR) results from extracted nucleic acid within one hour. In this study, reverse transcription iiPCR (RT-iiPCR) was developed to facilitate point-of-need diagnosis of CDV infection. RESULTS: Analytical sensitivity (limit of detection 95%) of the established CDV RT-iiPCR was about 11 copies of in vitro transcribed RNA per reaction. CDV RT-iiPCR generated positive signals from CDV, but not Bordetella bronchiseptica, canine parvovirus, canine herpesvirus, canine adenovirus 2, canine influenza virus (subtype H3N8), canine parainfluenza virus, and canine respiratory coronavirus. To evaluate accuracy of the established reaction in canine distemper clinical diagnosis, 110 specimens from dogs, raccoons, and foxes suspected with CDV infection were tested simultaneously by CDV RT-iiPCR and real-time RT-PCR. CDV RT-iiPCR demonstrated excellent sensitivity (100%) and specificity (100%), compared to real-time RT-PCR. CONCLUSIONS: The results indicated an excellent correlation between RT-iiPCR and a reference real time RT-PCR method. Working in a lyophilized format, the established method has great potential to be used for point-of-care diagnosis of canine distemper in animals, especially in resource-limited facilities.


title: Use of the Smartphone and Self-Concept in University Students According to the Gender Variable

text: The university stage comprises a very important and vital period in the modification of students’ lifestyles, and these changes can affect their self-concept. The excessive use of technology today can also influence the formation of their identity. The aim of this study is to analyze the relationship between self-concept and the use of the smartphone by university students in terms of gender. The sample included 253 students (mean age 21.39 ± 3.27) of the Primary Education Degree of the University of Jaén (106 men and 147 women). A questionnaire was used to unify several instruments: a sociodemographic questionnaire, a Self-Concept Form-5 questionnaire (AF-5), and a questionnaire on cell phone-related experiences (CERM). The results show the existence of significant differences between both genders in the academic, emotional, and social dimensions of self-concept, with women showing a greater academic self-concept and men showing an emotional and physical one. Regarding the use of the smartphone in relation to self-concept, significant differences are found in the academic and emotional dimensions depending on the degree of use. In addition, in relation to the use of the smartphone, it has been detected that half of the students present potential problems. It is concluded that there is a relationship between both constructs, especially the academic and emotional self-concept.


title: Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP‐1 and NF‐κB

text: Infection with different picornaviruses can cause meningitis/encephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astrocytes was investigated following infection with Theiler's murine encephalomyelitis virus (TMEV), coxsackievirus B3 (CVB3), or coxsackievirus B4 (CVB4). We report that all these viruses are potent inducers for the expression of interleukin‐8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) genes in primary human astrocytes, as well as in an established astrocyte cell line (U‐373MG). Further studies indicated that both activator protein‐1 (AP‐1) and NF‐κB transcription factors are required in the activation of chemokine genes in human astrocytes infected with various picornaviruses. Interestingly, the pattern of activated chemokine genes in human astrocytes is quite restricted compared to that in mouse astrocytes infected with the same viruses, suggesting species differences in gene activation. This may result in potential differences in the pathogenic outcome in each species. © 2003 Wiley‐Liss, Inc.


Wenn Viren viral gehen


title: Causes of fever in Gabonese children: a cross-sectional hospital-based study

text: The causes of infections in pediatric populations differ between age groups and settings, particularly in the tropics. Such differences in epidemiology may lead to misdiagnosis and ineffective empirical treatment. Here, we investigated the current spectrum of pathogens causing febrile diseases leading to pediatric hospitalization in Lambaréné, Gabon. From August 2015 to March 2016, we conducted a prospective, cross-sectional, hospital-based study in a provincial hospital. Patients were children ≤ 15 years with fever ≥ 38 °C and required hospitalization. A total of 600 febrile patients were enrolled. Malaria was the main diagnosis found in 52% (311/600) patients. Blood cultures revealed septicemia in 3% (17/593), among them four cases of typhoid fever. The other causes of fever were heterogeneously distributed between both bacteria and viruses. Severe infections identified by Lambaréné Organ Dysfunction Score (LODS) were also most often caused by malaria, but children with danger signs did not have more coinfections than others. In 6% (35/600) of patients, no pathogen was isolated. In Gabon, malaria is still the major cause of fever in children, followed by a bacterial and viral disease. Guidelines for both diagnosis and management should be tailored to the spectrum of pathogens and resources available locally.


title: The network effect: studying COVID-19 pathology with the Human Cell Atlas

text: The SARS coronavirus 2 (SARS-CoV-2) pandemic is a global challenge, which the scientific community has tackled by mounting extensive global collaborations, combining expertise in diverse areas and applying cutting-edge techniques, to dissect mechanisms underlying coronavirus disease-19 (COVID-19) pathology. The Human Cell Atlas consortium is emerging as an important contributor to furthering this progress.


title: Emerging challenges in urban waste management in Tehran, Iran during the COVID-19 pandemic

text: • New challenges in MSW management in Tehran after the COVID-19 pandemic was studied. • Over 5.5 millions of PPEs are being daily discarded in Tehran during COVID-19. • Hospital wastes are being disposed of without undergoing any treatment in Tehran. • Landfilling of MSW has increased by 34.7% after the outbreak of COVID-19. • Secondary contagion from improper management of MSW is probable in Tehran.


title: Identification of Neutralizing Monoclonal Antibodies Targeting Novel Conformational Epitopes of the Porcine Epidemic Diarrhoea Virus Spike Protein

text: Since 2010, newly identified variants of porcine epidemic diarrhoea virus (PEDV) have caused high mortality in neonatal piglets which has devastated the swine industry. The spike (S) glycoprotein of PEDV contains multiple neutralizing epitopes and is a major target for PEDV neutralization and vaccine development. To understand the antigenicity of the new PEDV variant, we characterized the neutralizing epitopes of a new genotype 2b PEDV isolate from Taiwan, PEDV Pintung 52 (PEDV-PT), by the generation of neutralizing monoclonal antibodies (NmAbs). Two NmAbs, P4B-1, and E10E-1–10 that recognized the ectodomain of the full-length recombinant PEDV S protein and exhibited neutralizing ability against the PEDV-PT virus were selected. Recombinant truncated S proteins were used to identify the target sequences for the NmAbs and P4B-1 was shown to recognize the C-terminus of CO-26K equivalent epitope (COE) at amino acids (a.a.) 575–639 of the PEDV S. Interestingly, E10E-1–10 could recognize a novel neutralizing epitope at a.a. 435–485 within the S1(A) domain of the PEDV S protein, whose importance and function are yet to be determined. Moreover, both NmAbs could not bind to linearized S proteins, indicating that only conformational epitopes are recognized. This data could improve our understanding of the antigenic structures of the PEDV S protein and facilitate future development of novel epitope-based vaccines.


title: Pandemic risk: how large are the expected losses?

text: There is an unmet need for greater investment in preparedness against major epidemics and pandemics. The arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. Recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. This produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. We parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about 720 000 per year. We calculated that the expected annual losses from pandemic risk to be about 500 billion United States dollars – or 0.6% of global income – per year. This estimate falls within – but towards the lower end of – the Intergovernmental Panel on Climate Change’s estimates of the value of the losses from global warming, which range from 0.2% to 2% of global income. The estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over 0.3% in high-income countries to 1.6% in lower-middle-income countries. Most of the losses from influenza pandemics come from rare, severe events.


title: Development of price models for architectural and environmental quality for residential developments in Hong Kong

text: Factors affecting a residential unit's price are always of interest to homebuyers and building developers, especially in a city like Hong Kong which is known for expensive housing. Literature review indicates that the governing factors can be categorized into architectural and environmental attributes. Among different methods commonly used for pricing, the hedonic price approach is viewed as the most suitable. However, the successful use of this method requires that homebuyers know and choose the attributes. Whilst choosing architectural attributes are not a problem for homebuyers, the same does not apply to environmental attributes. Previous studies by the authors have proposed some simple indicators for quantifying the environmental attributes. Based upon the developed performance indicators and the transaction records of two representative housing estates (Royal Ascot = RA and City One Shatin = COS), details of the properties, including transaction prices, architectural particulars and environmental characteristics were numerically transformed for the hedonic price analysis. The analysis results revealed that the willingness to pay (percentage of house price in parenthesis) for architectural and environmental attributes was HK$302.3/ft(2) (5.8%) and HK$886.8/ft(2) (28.2%), respectively, for RA and HK$1672.7/ft(2) (31.9%) and HK$111.5/ft(2) (3.5%) for COS. It was found that elasticity of substitution (ES) of environmental attributes contributed 3.4–13.3% of the property price, compared to 0.6–5.5% for architectural attributes.


title: Evaluation of rapid antigen test for detection of SARS-CoV-2 virus

text: BACKGROUND: The rapid diagnosis of COVID-19 patients is essential to reduce the disease spread. Rapid antigen detection (RAD) tests are available, however, there is scanty data on the performance of RAD tests. OBJECTIVE: To evaluate the performance of BIOCREDIT COVID-19 Ag test and compared it with real-time RT-PCR for detecting SARS-CoV-2 virus. Study Design: Analytical sensitivity for the detection of SARS-CoV-2 virus was determined for the RAD test using viral culture and PCR as a reference methods. The RAD test was further evaluated using respiratory samples collected from confirmed COVID-19 patients. The results were compared with RT-PCR test. RESULTS: The detection limits between RAD test, viral culture and PCR varied hugely. RAD was 103 fold less sensitive than viral culture while RAD was 105 fold less sensitive than RT-PCR. The RAD test detected between 11.1% and 45.7% of real-time RT-PCR-positive samples from COVID-19 patients. CONCLUSIONS: This study demonstrated that the RAD test serve only as adjunct to RT-PCR test because of potential for false-negative results.


title: Hyperpyrexia and metabolic alkalosis in a COVID‐19 patient

text: Hyperpyrexia can be a challenging and serious complication of SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Summarizing US Wildlife Trade with an Eye Toward Assessing the Risk of Infectious Disease Introduction

text: The aim of this study was to characterize the role of the USA in the global exchange of wildlife and describe high volume trade with an eye toward prioritizing health risk assessment questions for further analysis. Here we summarize nearly 14 years (2000–2013) of the most comprehensive data available (USFWS LEMIS system), involving 11 billion individual specimens and an additional 977 million kilograms of wildlife. The majority of shipments contained mammals (27%), while the majority of specimens imported were shells (57%) and tropical fish (25%). Most imports were facilitated by the aquatic and pet industry, resulting in one-third of all shipments containing live animals. The importer reported origin of wildlife was 77.7% wild-caught and 17.7% captive-reared. Indonesia was the leading exporter of legal shipments, while Mexico was the leading source reported for illegal shipments. At the specimen level, China was the leading exporter of legal and illegal wildlife imports. The number of annual declared shipments doubled during the period examined, illustrating continually increasing demand, which reinforces the need to scale up capacity for border inspections, risk management protocols and disease surveillance. Most regulatory oversight of wildlife trade is aimed at conservation, rather than prevention of disease introduction.


title: Pediatrics in 21(st) Century and Beyond

text: Pediatrics is a dynamic discipline and there is awareness and hope for actualizing outstanding achievements in the field of child health in 21(st) century and beyond. Improved lifestyle and quality of children’s health is likely to reduce the burden of adult diseases and enhance longevity because seeds of most adult diseases are sown in childhood. Identification and decoding of human genome is expected to revolutionize the practice of pediatrics. The day is not far off when a patient will walk into doctor’s chamber with an electronic or digital health history on a CD or palmtop and a decoded genomic constitution. There will be reduced burden of genetic diseases because of selective abortions of “defective” fetuses and replacement of “bad” genes with “good” ones by genetic engineering. Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. The possibility of producing flawless designer babies by advances in assisted reproductive technologies (ARTs) is likely to be mired by several ethical and legal issues. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. There is going to be a greater focus on the “patient” having the disease rather than “disease” per se by practicing holistic pediatrics by effective utilization of alternative or complementary strategies for health care. Due to advances in technology, pediatrics may get further dehumanized. A true healer cannot simply rely on technology; there must be a spiritual bond between the patient and the physician by exploiting the concept of psycho-neuro-immunology and body-mind interactions. In the years to come, physicians are likely to play “god” but medicine can’t achieve immortality because anything born must die in accordance with nature’s recycling blueprint. The medical science is likely to improve longevity but our goal should be to improve the quality of life.


title: Isolation and characterization of dengue virus serotype 2 from the large dengue outbreak in Guangdong, China in 2014

text: Dengue has been well recognized as a global public health threat, but only sporadic epidemics and imported cases were reported in recent decades in China. Since July 2014, an unexpected large dengue outbreak has occurred in Guangdong province, China, resulting in more than 40000 patients including six deaths. To clarify and characterize the causative agent of this outbreak, the acute phase serum from a patient diagnosed with severe dengue was subjected to virus isolation and high-throughput sequencing (HTS). Traditional real-time RT-PCR and HTS with Ion Torrent PGM detected the presence of dengue virus serotype 2 (DENV-2). A clinical DENV-2 isolate GZ05/2014 was obtained by culturing the patient serum in mosquito C6/36 cells. The complete genome of GZ05/2014 was determined and deposited in GenBank under the access number KP012546. Phylogenetic analysis based on the complete envelope gene showed that the newly DENV-2 isolate belonged to Cosmopolitan genotype and clustered closely with other Guangdong strains isolated in the past decade. No amino acid mutations that are obviously known to increase virulence or replication were identified throughout the genome of GZ05/2014. The high homology of Guangdong DENV-2 strains indicated the possibility of establishment of local DENV-2 circulation in Guangdong, China. These results help clarify the origin of this epidemic and predict the future status of dengue in China. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-014-4782-3 and is accessible for authorized users.


title: Public health human resources: a comparative analysis of policy documents in two Canadian provinces

text: BACKGROUND: Amidst concerns regarding the capacity of the public health system to respond rapidly and appropriately to threats such as pandemics and terrorism, along with changing population health needs, governments have focused on strengthening public health systems. A key factor in a robust public health system is its workforce. As part of a nationally funded study of public health renewal in Canada, a policy analysis was conducted to compare public health human resources-relevant documents in two Canadian provinces, British Columbia (BC) and Ontario (ON), as they each implement public health renewal activities. METHODS: A content analysis of policy and planning documents from government and public health-related organizations was conducted by a research team comprised of academics and government decision-makers. Documents published between 2003 and 2011 were accessed (BC = 27; ON = 20); documents were either publicly available or internal to government and excerpted with permission. Documentary texts were deductively coded using a coding template developed by the researchers based on key health human resources concepts derived from two national policy documents. RESULTS: Documents in both provinces highlighted the importance of public health human resources planning and policies; this was particularly evident in early post-SARS documents. Key thematic areas of public health human resources identified were: education, training, and competencies; capacity; supply; intersectoral collaboration; leadership; public health planning context; and priority populations. Policy documents in both provinces discussed the importance of an educated, competent public health workforce with the appropriate skills and competencies for the effective and efficient delivery of public health services. CONCLUSION: This policy analysis identified progressive work on public health human resources policy and planning with early documents providing an inventory of issues to be addressed and later documents providing evidence of beginning policy development and implementation. While many similarities exist between the provinces, the context distinctive to each province has influenced and shaped how they have focused their public health human resources policies.


Expanding the use of alternative models to investigate novel aspects of immunity to microbial pathogens


title: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

text: BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)


title: Sensitive and specific detection of strains of Japanese encephalitis virus using a one‐step TaqMan RT‐PCR technique

text: A rapid, sensitive, and accurate laboratory diagnostic test is needed for distinguishing Japanese encephalitis virus (JEV) from other diseases featuring similar clinical symptoms and also for preventing potential outbreaks. In this study, a TaqMan reverse transcription (RT)‐polymerase chain reaction (PCR) assay was developed for rapid detection and quantification of the viral RNA of various JEV strains. A consensus JEV NS3 region was chosen to design the primers and the TaqMan probe. The JEV TaqMan assay used the EZ‐rTtH RT‐PCR system featuring advantages such as a one‐step, high‐temperature RT reaction modality and preventing carry‐over contamination. The sensitivity of the JEV TaqMan assay for detecting in vitro‐transcribed JEV NS3 RNA was estimated to be one to five copies of RNA per reaction. For cultured JE virions, less than 40 plaque forming unit (PFU)/ml of virus load (corresponding to 0.07 PFU/test) could be detected. In addition, the JEV TaqMan assay could detect all seven strains of JEV tested, but provided negative results for nine other flaviviruses and encephalitis viruses tested. The JEV TaqMan assay demonstrated greater sensitivity and specificity than traditional RT‐PCR methods as has been previously reported. The application of the JEV TaqMan assay herein has been shown to the sensitive detection of the JEV from both mosquito pools and also JEV‐spiking human blood. The assay should be of use in diagnostic laboratory conduct and could be used to replace or complement time‐consuming viral‐culture methods, thus achieving more rapid, sensitive, and highly specific identification of JEV infection. J. Med. Virol. 74:589–596, 2004. © 2004 Wiley‐Liss, Inc.


title: Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs

text: SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a. In related SARS-CoV-1, 3a is implicated in viral release, inflammasome activation, and cell death and its deletion reduces viral titer and morbidity in animal models, suggesting 3a-targeted therapeutics could treat SARS and COVID-19. However, the structural basis for the function of 3a is unknown. Here, we show that SARS-CoV-2 forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric SARS-CoV-2 3a in lipid nanodiscs. 3a adopts a novel fold and is captured in a closed or inactivated state. A narrow bifurcated exterior pore precludes conduction and leads to a large polar cavity open to the cytosol. 3a function is conserved in a common variant among circulating SARS-CoV-2 that alters the channel pore. We identify 3a-like proteins in Alpha- and Beta-coronaviruses that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.


Complicated coronavirus disease 2019 (COVID‐19) in a psoriatic patient treated with ixekizumab


title: The impact of PD-L1 N-linked glycosylation on cancer therapy and clinical diagnosis

text: N-linked glycosylation is one of the most abundant posttranslational modifications of membrane-bound proteins in eukaryotes and affects a number of biological activities, including protein biosynthesis, protein stability, intracellular trafficking, subcellular localization, and ligand-receptor interaction. Accumulating evidence indicates that cell membrane immune checkpoint proteins, such as programmed death-ligand 1 (PD-L1), are glycosylated with heavy N-linked glycan moieties in human cancers. N-linked glycosylation of PD-L1 maintains its protein stability and interaction with its cognate receptor, programmed cell death protein 1 (PD-1), and this in turn promotes evasion of T-cell immunity. Studies have suggested targeting PD-L1 glycosylation as a therapeutic option by rational combination of cancer immunotherapies. Interestingly, structural hindrance by N-glycan on PD-L1 in fixed samples impedes its recognition by PD-L1 diagnostic antibodies. Notably, the removal of N-linked glycosylation enhances PD-L1 detection in a variety of bioassays and more accurately predicts the therapeutic efficacy of PD-1/PD-L1 inhibitors, suggesting an important clinical implication of PD-L1 N-linked glycosylation. A detailed understanding of the regulatory mechanisms, cellular functions, and diagnostic limits underlying PD-L1 N-linked glycosylation could shed new light on the clinical development of immune checkpoint inhibitors for cancer treatment and deepen our knowledge of biomarkers to identify patients who would benefit the most from immunotherapy. In this review, we highlight the effects of protein glycosylation on cancer immunotherapy using N-linked glycosylation of PD-L1 as an example. In addition, we consider the potential impacts of PD-L1 N-linked glycosylation on clinical diagnosis. The notion of utilizing the deglycosylated form of PD-L1 as a predictive biomarker to guide anti-PD-1/PD-L1 immunotherapy is also discussed.


title: Applying the Lessons of SARS to Pandemic Influenza: An Evidence-based Approach to Mitigating the Stress Experienced by Healthcare Workers

text: We describe an evidence-based approach to enhancing the resilience of healthcare workers in preparation for an influenza pandemic, based on evidence about the stress associated with working in healthcare during the SARS outbreak. SARS was associated with significant long-term stress in healthcare workers, but not with increased mental illness. Reducing pandemic-related stress may best be accomplished through interventions designed to enhance resilience in psychologically healthy people. Applicable models to improve adaptation in individuals include Folkman and Greer’s framework for stress appraisal and coping along with psychological first aid. Resilience is supported at an organizational level by effective training and support, development of material and relational reserves, effective leadership, the effects of the characteristics of “magnet hospitals,” and a culture of organizational justice. Evidence supports the goal of developing and maintaining an organizational culture of resilience in order to reduce the expected stress of an influenza pandemic on healthcare workers. This recommendation goes well beyond the provision of adequate training and counseling. Although the severity of a pandemic is unpredictable, this effort is not likely to be wasted because it will also support the health of both patients and staff in normal times.


Inhibition and Escape of SARS-CoV Treated with Antisense Morpholino Oligomers


title: Paramyxoviruses of Animals

text: Paramyxoviruses (some of which are also called parainfluenza viruses) cause a wide variety of diseases in animals. Many paramyxoviruses cause primarily respiratory disease, while others cause serious systemic disease. Many diseases caused by animal paramyxoviruses also have a neurological component or a reproductive disease component. Several of the most devastating diseases of animals, such as rinderpest, Newcastle disease, and canine distemper, are caused by paramyxoviruses. Some of the animal paramyxoviruses, such as the Hendra and Nipah viruses, are emerging zoonotic pathogens of major public health concern. New paramyxoviruses are being isolated on a continuing basis from a wide variety of animals. All animal paramyxoviruses belong to the family Paramyxoviridae. The members of this virus family are enveloped and have genomes consisting of a single segment of negative-sense RNA that contains 6–10 genes encoding up to 12 proteins. Although there are many animal paramyxoviruses, only a few effective vaccines are currently available. In the last decade, methods of producing many animal paramyxoviruses entirely from cDNA clones (reverse genetics) have been developed. This has not only greatly improved our understanding of the molecular biology and pathogenesis of these viruses, but has also made it possible to engineer improved vaccines for them.


title: Use of Transgenic Animals to Improve Human Health and Animal Production

text: Transgenic animals are more widely used for various purposes. Applications of animal transgenesis may be divided into three major categories: (i) to obtain information on gene function and regulation as well as on human diseases, (ii) to obtain high value products (recombinant pharmaceutical proteins and xeno‐organs for humans) to be used for human therapy, and (iii) to improve animal products for human consumption. All these applications are directly or not related to human health. Animal transgenesis started in 1980. Important improvement of the methods has been made and are still being achieved to reduce cost as well as killing of animals and to improve the relevance of the models. This includes gene transfer and design of reliable vectors for transgene expression. This review describes the state of the art of animal transgenesis from a technical point of view. It also reports some of the applications in the medical field based on the use of transgenic animal models. The advance in the generation of pigs to be used as the source of organs for patients and in the preparation of pharmaceutical proteins from milk and other possible biological fluids from transgenic animals is described. The projects in course aiming at improving animal production by transgenesis are also depicted. Some the specific biosafety and bioethical problems raised by the different applications of transgenesis, including consumption of transgenic animal products are discussed.


title: Are trans‐complementation systems suitable for hepatitis C virus life cycle studies?

text: Complementation is a naturally occurring genetic mechanism that has been studied for a number of plus‐strand RNA viruses. Although trans‐complementation is well documented for Flaviviridae family viruses, the first such system for hepatitis C virus (HCV) was only described in 2005. Since then, the development of a number of HCV trans‐complementation models has improved our knowledge of HCV protein functions and interactions, genome replication and viral particle assembly. These models have also been used to produce defective viruses and so improvements are necessary for vaccine assays. This review provides an update on HCV trans‐complementation systems, the viral mechanisms studied therewith and the production and characterization of trans‐encapsidated particles.


Table des matieres


Please cite this paper as: Salmón‐Mulanovich et al. (2010) Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru. Influenza and Other Respiratory Viruses 5(1), 1–5. Background Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified. Objectives Our study aimed to estimate the frequency of human bocavirus (HBoV) infection among pediatric populations in Argentina, Nicaragua and Peru. Methods We conducted a cross‐sectional study using stored samples of an influenza‐like illness surveillance program. Irrespective of previous diagnosis, nasopharyngeal or nasal swab specimens were randomly selected and tested using real‐time PCR from three sites during 2007 from patients younger than 6 years old. Results A total of 568 specimens from Argentina (185), Nicaragua (192) and Peru (191) were tested. The prevalence of HBoV was 10·8% (95% CI: 6·3; 15·3) in Argentina, 33·3% in Nicaragua (95% CI: 26·6; 40·1) and 25·1% in Peru (95% CI: 18·9; 31·3). Conclusions These findings demonstrate circulation of HBoV in Argentina, Nicaragua and Peru among children with influenza‐like symptoms enrolled in a sentinel surveillance program.


title: Babesia vesperuginis in insectivorous bats from China

text: BACKGROUND: To increase understanding of human bacterial and parasitic pathogens in bats, we investigated the prevalence of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii in bats from China. METHODS: Bats were captured from Mengyin County, Shandong Province of China using nets. DNA was extracted from the blood and spleen of bats for molecular detection of Babesia spp., Rickettsia spp., Anaplasma spp. and Coxiella burnetii with specific primers for each species. RESULTS: A total of 146 spleen samples and 107 blood samples of insectivorous bats, which belonged to 6 species within two families, were collected from Mengyin County, Shandong Province of China. We found that two Eptesicus serotinus (2/15, 13.3%) were positive for Babesia vesperuginis. We were unable to detect genomic sequences for Rickettsia spp., Anaplasma spp. and Coxiella burnetii. CONCLUSIONS: To our knowledge, our study showed for the first time the presence of Babesia vesperuginis in Eptesicus serotinus collected from China, suggesting that Babesia vesperuginis has a broad host species and geographical distribution.


title: Do Newton’s rules of reasoning guarantee truth … must they?

text: Abstract Newton’s Principia introduces four rules of reasoning for natural philosophy. Although useful, there is a concern about whether Newton’s rules guarantee truth. After redirecting the discussion from truth to validity, I show that these rules are valid insofar as they fulfill Goodman’s criteria for inductive rules and Newton’s own methodological program of experimental philosophy; provided that cross-checks are used prior to applications of rule 4 and immediately after applications of rule 2 the following activities are pursued: (1) research addressing observations that systematically deviate from theoretical idealizations and (2) applications of theory that safeguard ongoing research from proceeding down a garden path.


title: Chapter 4 Replication

text: This chapter provides an overview of the key stages in virus replication, including the historic experiments which resulted in our present understanding. It describes, step by step, how replication unfolds, starting with the initial interaction between the virus and a host cell and finishing with the release of infectious virus particles which can go on and infect new cells. Since these processes are essential in the replication cycle, understanding how they can be blocked specifically without damaging the host cell is the key to understanding how antiviral drugs work.


title: Obstetric Anesthesia During the Coronavirus Disease 2019 Pandemic

text: With increasing numbers of Coronavirus Disease 2019 (COVID19) cases due to efficient human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States, preparation for the unpredictable setting of labor and delivery is paramount. The priorities are 2-fold in the management of obstetric patients with COVID-19 infection or persons under investigation (PUI): (1) caring for the range of asymptomatic to critically ill pregnant and postpartum women; (2) protecting health care workers and beyond from exposure during the delivery hospitalization (health care providers, personnel, family members). The goal of this review is to provide evidence-based recommendations or, when evidence is limited, expert opinion for anesthesiologists caring for pregnant women during the COVID19 pandemic with a focus on preparedness and best clinical obstetric anesthesia practice.


Recommandations de la Société Française de Médecine du Travail (SFMT): le formol 4% est-il virucide sur le COVID-19? Au bout de combien de temps de fixation? 27 mars 2020


title: Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

text: BACKGROUND: Mesenchymal stem (stromal) cells (MSCs) mediate their immunoregulatory and tissue repair functions by secreting paracrine factors, including extracellular vesicles (EVs). In several animal models of human diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause annual outbreaks of acute respiratory illness resulting in significant mortality and morbidity. Influenza viruses constantly evolve, thus generating drug-resistant strains and rendering current vaccines less effective against the newly generated strains. Therefore, new therapies that can control virus replication and the inflammatory response of the host are needed. The objective of this study was to examine if MSC-EV treatment can attenuate influenza virus-induced acute lung injury in a preclinical model. METHODS: We isolated EVs from swine bone marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy and expression of mesenchymal markers was examined by flow cytometry. Next, we examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells and anti-viral and immunomodulatory properties in vivo in a pig model of influenza virus. RESULTS: MSC-EVs were isolated from MSC-conditioned medium by ultracentrifugation. MSC-EVs were round-shaped and, similarly to MSCs, expressed mesenchymal markers and lacked the expression of swine leukocyte antigens I and II. Incubation of PKH-26-labeled EVs with lung epithelial cells revealed that MSC-EVs incorporated into the epithelial cells. Next, we examined the anti-influenza and anti-inflammatory properties of MSC-EVs. MSC-EVs inhibited the hemagglutination activity of avian, swine, and human influenza viruses at concentrations of 1.25–5 μg/ml. MSC-EVs inhibited influenza virus replication and virus-induced apoptosis in lung epithelial cells. The anti-influenza activity of MSC-EVs was due to transfer of RNAs from EVs to epithelial cells since pre-incubation of MSC-EVs with RNase enzyme abrogated the anti-influenza activity of MSC-EVs. In a pig model of influenza virus, intratracheal administration of MSC-EVs 12 h after influenza virus infection significantly reduced virus shedding in the nasal swabs, influenza virus replication in the lungs, and virus-induced production of proinflammatory cytokines in the lungs of influenza-infected pigs. The histopathological findings revealed that MSC-EVs alleviated influenza virus-induced lung lesions in pigs. CONCLUSIONS: Our data demonstrated in a relevant preclinical large animal model of influenza virus that MSC-EVs possessed anti-influenza and anti-inflammatory properties and that EVs may be used as cell-free therapy for influenza in humans.


title: Acute Neurological Care in the COVID-19 Era: The Pandemic Health System REsilience PROGRAM (REPROGRAM) Consortium Pathway

text: The management of acute neurological conditions, particularly acute ischemic stroke, in the context of Coronavirus disease 2019 (COVID-19), is of importance, considering the risk of infection to the healthcare workers and patients and emerging evidence of the neuroinvasive potential of the virus. There are variations in expert guidelines further complicating the picture for clinicians in acute settings. In this light, there is a compelling need for further formulation of recommendations that compile these variations seen in the numerous guidelines present. Health system protocols for managing ongoing acute neurological care and intervention need consideration of safety and well-being of the frontline healthcare workers and the patients. We examine existing pathways and their efficacy to mitigate viral exposure to the healthcare workers and patients and synthesize a systemic approach to manage patients with acute neurological conditions in the COVID-19 scenario. Early experiences with a COVID-19 positive stroke patient treated with endovascular thrombectomy is presented to highlight the urgent need for adequate personal protective equipment (PPE) during acute neuro-interventional procedures.


title: Rapid guide to the management of cardiac patients during the COVID-19 pandemic in Egypt: “a position statement of the Egyptian Society of Cardiology”

text: COVID-19 pandemic poses an enormous challenge to healthcare system in Egypt. This document is a position statement from the Egyptian Society of Cardiology. It aims to provide information to cardiovascular healthcare providers in Egypt to guarantee delivery of quality patient care and ensure adequate levels of protection against infection during the COVID-19 pandemic. Older patients and those with cardiovascular disease are at higher risk of mortality. The current situation requires unusual allocation of resources which may negatively impact the care of patients with cardiovascular disease. Cardiologists should be prepared in the COVID-19 pandemic. The challenge is in providing the best quality of care despite limited resources while keeping all medical staff as safe as possible. Consider deferring elective procedures whenever possible. All medical staff should undergo rigorous training on infection control and the use of high-quality personal protection equipment. Cardiologists should promote telemedicine in the outpatient setting, prioritize outpatient contacts, and avoid nosocomial dissemination of the virus to patients and healthcare providers. A much conservative approach for emergent cardiac patients is recommended, and invasive interventions are reserved for high risk hemodynamically unstable patients. During the pandemic, the most important principles of treatment should be controlling the spread of infection as the first priority, prompt assessment of patient risk, recommending conservative medical therapy rather than invasive interventions, and strict infection control measures to limit infection spread within the hospital and to healthcare workers.


title: Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas

text: Viral infections cause at least 10%–15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.


title: Frequency of respiratory virus infections and next-generation analysis of influenza A/H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU

text: Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs). It has been observed that 222G/N changes in the HA gene of H1N1pdm09 are associated with increased lower respiratory tract (LRT) replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014–2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4%) patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6%) were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2), 8/69 (11.6%) for HRV, 2/69 (2.9%) for RSV and 2/69 (2.9%) for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT) (p<0.05). Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180–286) in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.


title: Preliminary study on the tick population of Benin wildlife at the moment of its invasion by the Rhipicephalus microplus tick (Canestrini, 1888)

text: BACKGROUND AND AIM: Rhipicephalus microplus (Rm) is one of the most problematic livestock tick species in the world. Its rapid propagation and resistance to acaricides make it control difficult in the sub-region and Benin particularly. The aim of this work was to check its presence in wildlife and to confirm the possible role of reservoir wildlife may play in the propagation of the parasite. This will help to design more efficient control strategy. MATERIALS AND METHODS: This study was conducted from February to March 2017 in the National Parks of Benin (Pendjari and W Park) and wildfowl’s assembly and selling point in Benin. Ticks were manually picked with forceps from each animal after slaughtering by hunters then stored in 70° ethanol. Collected ticks were counted and identified in the laboratory using the identification key as described by Walker. RESULTS: Overall, seven species of ticks (Amblyomma variegatum, Boophilus decoloratus, Rm, Boophilus spp., Hyalomma spp., Rhipicephalus sanguineus, Rhipicephalus spp.) were identified on nine wild animal species sampled (Cane rat, wildcat, Hare, Doe, Cricetoma, Buffalo, Buffon Cobe, and Bushbuck and Warthog). The average number of ticks varies from 3 to 6 between animal species, 3 to 7 between localities visited, and 2 to 5 between tick species. However, these differences are statistically significant only for localities. Considering tick species and animal species, the parasite load of Rm and Rhipicephalus spp. is higher; the buffalo being more infested. The analysis of deviance reveals that the abundance of ticks observed depends only on the observed localities (p>0.05). However, the interactions between animal species and localities on the one hand and between animal and tick species on the other hand, although not significant, have influenced the abundance of ticks as they reduce the residual deviance after their inclusion in the model. CONCLUSIONS: This study reported the presence of Rm in wildlife of Benin and confirmed its role in the maintenance and spread of the parasites. It is, therefore, an important risk factor that we must not neglect in the epidemiological surveillance and ticks control strategies in the West African sub-region and particularly in Benin.


title: Providing nutritional care to cancer patients during the COVID-19 pandemic: an Italian perspective

text: The COVID-19 outbreak has drastically changed practices inside hospitals, which include oncology routines. In oncology, malnutrition was and certainly still is a frequent problem associated with an increase in treatment-related toxicity, a reduced response to cancer treatment, an impaired quality of life, and a worse overall prognosis. Even in this situation of healthcare crisis, nutritional support in cancer care is an essential element. During the current COVID-19 pandemic, there is a concrete high risk to see a dramatic worsening of cancer patients’ nutritional status, who are left without adequate clinical and nutritional support. The consequences are already reasonably foreseeable and will have a severe negative impact after the emergency. Therefore, we believe that it is essential to try to continue, as far as possible, the activity of clinical nutrition in oncology, by revolutionizing the setting and the approach to patients. For this purpose, the Clinical Nutrition and Dietetics Unit and the Medical Oncology Unit of our hospital, one of the largest community hospital in Lombardy that has been involved in the COVID-19 outbreak management since its inception, have reorganized the clinical routine activity in strict collaboration since the very beginning of the emergency, to better face up to the challenge, while preserving cancer patients’ needs.


title: Heparin‐binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients

text: Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin‐binding protein (HBP), lysozyme, and the cytokines interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung‐transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL‐1β, and IL‐8 were the best diagnostic markers of infection with area under the receiver‐operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL‐1β, and IL‐8 could be useful diagnostic markers of pulmonary infection in lung‐transplanted patients.


title: Airflow Decline after Myeloablative Allogeneic Hematopoietic Cell Transplantation: The Role of Community Respiratory Viruses

text: We conducted a 12-year retrospective study to determine the effects that the community respiratory-virus species and the localization of respiratory-tract virus infection have on severe airflow decline, a serious and fatal complication occurring after hematopoietic cell transplantation (HCT). Of 132 HCT recipients with respiratory-tract virus infection during the initial 100 days after HCT, 50 (38%) developed airflow decline ⩽1 year after HCT. Lower-respiratory-tract infection with parainfluenza (odds ratio [OR], 17.9 [95% confidence interval {CI}, 2.0–160]; P=.01) and respiratory syncytial virus (OR, 3.6 [95% CI, 1.0–13]; P=.05) independently increased the risk of development of airflow decline ⩽1 year after HCT. The airflow decline was immediately detectable after infection and was strongest for lower-respiratory-tract infection with parainfluenza virus; it stabilized during the months after the respiratory-tract virus infection, but, at ⩽1 year after HCT, the initial lung function was not restored. Thus, community respiratory virus–associated airflow decline seems to be specific to viral species and infection localization