title: Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract

text: Otitis media (OM) is a major burden for all children, particularly for Australian Aboriginal children. Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and viruses (including rhinovirus and adenovirus) are associated with OM. We investigated nasopharyngeal microbial interactions in 435 samples collected from 79 Aboriginal and 570 samples from 88 non-Aboriginal children in Western Australia. We describe a multivariate random effects model appropriate for analysis of longitudinal data, which enables the identification of two independent levels of correlation between pairs of pathogens. At the microbe level, rhinovirus infection was positively correlated with carriage of S. pneumoniae, H. influenzae and M. catarrhalis, and adenovirus with M. catarrhalis. Generally, there were positive associations between bacterial pathogens at both the host and microbe level. Positive viral–bacterial associations at the microbe level support previous findings indicating that viral infection can predispose an individual to bacterial carriage. Viral vaccines may assist in reducing the burden of bacterial disease.


title: The impact of long-term non-pharmaceutical interventions on COVID-19 epidemic dynamics and control

text: Non-pharmaceutical interventions to combat COVID-19 transmission have worked to slow the spread of the epidemic but can have high socio-economic costs. It is critical we understand the efficacy of non-pharmaceutical interventions to choose a safe exit strategy. Many current models are not suitable for assessing exit strategies because they do not account for epidemic resurgence when social distancing ends prematurely (e.g., statistical curve fits) nor permit scenario exploration in specific locations. We developed an SEIR-type mechanistic epidemiological model of COVID-19 dynamics to explore temporally variable non-pharmaceutical interventions. We provide an interactive tool and code to estimate the transmission parameter, β, and the effective reproduction number, [Formula: see text]. We fit the model to Santa Clara County, California, where an early epidemic start date and early shelter-in-place orders could provide a model for other regions. As of April 22, 2020, we estimate an R(E) of 0.982 (95% CI: 0.849 – 1.107) in Santa Clara County. After June 1 (the end-date for Santa Clara County shelter-in-place as of April 27), we estimate a shift to partial social distancing, combined with rigorous testing and isolation of symptomatic individuals, is a viable alternative to indefinitely maintaining shelter-in-place. We also estimate that if Santa Clara County had waited one week longer before issuing shelter-in-place orders, 95 additional people would have died by April 22 (95% CI: 7 – 283). Given early life-saving shelter-in-place orders in Santa Clara County, longer-term moderate social distancing and testing and isolation of symptomatic individuals have the potential to contain the size and toll of the COVID-19 pandemic in Santa Clara County, and may be effective in other locations.


title: The role of Selectivity of the SARS-CoV-2 Virus for Human Genetic Profiles in Susceptibility and Resistance to COVID-19

text: Recently observed similarities in COVID-19 susceptibility among genetically related individuals hints at a selectivity of the SARS-CoV-2 virus that hinges on the affinity for select genetic profiles prevalent in the human species. The selectivity determines susceptibility of clinical disease and extent of pathogenesis, including fatal lung and myocardial injury, and may be more cogent than the recently reported risk factors. The selectivity of the SARS-CoV-2 virus for human genetic profiles as a factor of the virulence appears to be a novel feature and was not previously noted in the epidemics of widespread viral respiratory illnesses in humans.


title: DC/L‐SIGNs of Hope in the COVID‐19 Pandemic

text: In a rapidly evolving pandemic such as COVID‐19, theories which help unify disparate pre‐clinical and clinical observations would be useful. The current pandemic and its pleotropic effects can be explained in part by interaction between SARS‐CoV‐2 spike protein S, the ACE2/L‐SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC‐SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells. Infection of the DC by SARS‐CoV‐2 can potentially explain the exuberant distal immunopathology seen in COVID‐19. This article is protected by copyright. All rights reserved.


title: Controversies regarding shielding and susceptibility to COVID‐19 disease in liver transplant recipients in the United Kingdom

text: December 2019 saw the emergence of a novel coronavirus, SARS-CoV-2, which rapidly escalated to a global pandemic 1 , with an unprecedented impact on healthcare systems worldwide. The objective of this case series is to report on SARS-CoV-2 infection in liver transplant recipients and discuss the role of immunosuppression, comorbidities and shielding. In the UK, transplant recipients were classified as individuals vulnerable to SARS-CoV-2 infection due to immunosuppression. They were advised in late March 2020 (Figure 1) by Public Health England to take additional social distancing precautions, a process referred to as 'shielding' 2 . This is a more rigorous form of isolation that requires the individual to not leave their place of residence or come into contact with others. In essence, completely isolate to minimise the risk of being exposed to SARS-CoV-2.


title: A dual-functional paramyxovirus F protein regulatory switch segment: activation and membrane fusion

text: Many viral fusion–mediating glycoproteins couple α-helical bundle formation to membrane merger, but have different methods for fusion activation. To study paramyxovirus-mediated fusion, we mutated the SV5 fusion (F) protein at conserved residues L447 and I449, which are adjacent to heptad repeat (HR) B and bind to a prominent cavity in the HRA trimeric coiled coil in the fusogenic six-helix bundle (6HB) structure. These analyses on residues L447 and I449, both in intact F protein and in 6HB, suggest a metamorphic region around these residues with dual structural roles. Mutation of L447 and I449 to aliphatic residues destabilizes the 6HB structure and attenuates fusion activity. Mutation of L447 and I449 to aromatic residues also destabilizes the 6HB structure despite promoting hyperactive fusion, indicating that 6HB stability alone does not dictate fusogenicity. Thus, residues L447 and I449 adjacent to HRB in paramyxovirus F have distinct roles in fusion activation and 6HB formation, suggesting this region is involved in a conformational switch.


title: PEGylated human catalase elicits potent therapeutic effects on H1N1 influenza-induced pneumonia in mice

text: Therapeutic recombinant human catalase (rhCAT) can quench infection-induced reactive oxygen species (ROS), thereby alleviating the associated tissue damage. Although the intranasal route is efficient to deliver native rhCAT to the lung, the therapeutic effect is limited by rapid elimination from the blood. In this study, we modified rhCAT with the active polymer, polyethylene glycol monomethyl ether (PEG)-5000, and analyzed the pharmacokinetics of PEGylated rhCAT in mice. The high tetra-PEGylation ratio was about 60 %, and PEGylation prolonged the half-life of rhCAT in serum (75 vs. 13.5 min for native rhCAT). The protective effects of PEG-rhCAT were investigated in a mouse model of influenza virus A (H1N1)-associated pneumonia. PEG-rhCAT was more effectively delivered than native rhCAT and was associated with higher survival ratio, less extensive lung injuries, reduced ROS levels, and lower viral replication. Collectively, these findings indicate that PEGylation can enhance the therapeutic efficacy of native rhCAT and suggest that PEGylated rhCAT may represent a novel complement therapy for H1N1 influenza-induced pneumonia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-013-4775-3) contains supplementary material, which is available to authorized users.


title: Relationship Between ACE2 and Other Components of the Renin-Angiotensin System

text: PURPOSE OF THE REVIEW: Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection. RECENT FINDINGS: ACE2 converts angiotensin (Ang) II to Ang-(1–7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. ACE2 also facilitates SARS-CoV-2 viral entry into host cells. Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. SUMMARY: High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.


title: Sickle-cell disease in febrile children living in a rural village of Madagascar and association with malaria and respiratory infections

text: BACKGROUND: In Madagascar, the last study on sickle cell disease (SCD) was done in the early 1980s. The country is known as endemic for malaria and respiratory infections. The main objective of this study was to estimate the prevalence of SCD; the secondary objective was to evaluate its association with malaria and respiratory infections. METHODS: This is a cross-sectional study which was carried out in a rural village in the south east coast of Madagascar between May 2011 and November 2013. Participants were children aged between 2–59 months presenting with fever measured by axillary temperature ≥37.5 °C at inclusion. Genotyping of haemoglobin S was done by PCR and malaria was diagnosed by Rapid Diagnostic Test. Research for viral and atypical bacterial respiratory pathogens was performed on nasopharyngeal swabs. Uni-and multivariate polytomous logistic regression was done to assess associations between microbiological results and SCD status, with HbAA phenotype as reference. RESULTS: A total of 807 children were analysed. Prevalence of SCD among febrile children was 2.4% (95% CI, 1.5–3.7%) and that of SCT was 23.8% (95% CI, 20.9–26.9%). There was no difference in the prevalence of malaria infection according to haemoglobin status (p = 0.3). Rhinovirus (22.5%), adenovirus (14.1%), and bocavirus (11.6%) were the most common respiratory pathogens detected. After univariate analysis, patients with SCD were more frequently infected by parechovirus (p = 0.01), while patients with SCT were more prone to RSV A or B infection (p = 0.01). After multivariate analysis, HbAS phenotype was associated with higher risk of RSV A and B infection compared to HbAA (adjusted OR = 1.9; 95% CI: 1.2–3.1, p = 0.009), while HbSS phenotype was associated with higher risk of parechovirus infection (adjusted OR = 6.0; 95% CI: 1.1–31.3, p = 0.03) compared to HbAA, independently of age, gender, period per quarter, and the other viruses. CONCLUSION: The prevalence of SCD among under-five children presenting with fever was high in the study population. No association was found between SCT and malaria but few viruses, especially parechovirus, seem to play an important role in the occurrence of pneumoniae among SCD patients.


title: Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells

text: Therapeutic vaccination of lymphoma patients with tumor-specific immunoglobulin (idiotype, Id) coupled to the carrier protein keyhole limpet hemocyanin (Id-KLH) is undergoing clinical investigation, and methods to improve the immunogenicity of these and other protein tumor antigen vaccines are being sought. Id proteins can be produced via tumor-myeloma hybridomas or recombinant methods in mammalian, bacteria, or insect cells. We now demonstrate that terminal mannose residues, characteristic of recombinant proteins produced in insect cells, yield Id proteins with significantly enhanced immunostimulatory properties compared to Id proteins derived from mammalian cells. Recombinant baculovirus-infected insect cell-derived Id showed higher binding to and activation of human dendritic cells mediated by mannose receptors. In vivo, insect cell-derived Id elicited higher levels of tumor-specific CD8(+) CTL and improved eradication of pre-established murine lymphoma. Insect cell and mammalian Id generated similar levels of tumor-specific antibodies, showing no impairment in antibody responses to native tumor antigen despite the glycoslylation differences in the immunogen. Combining insect cell production and maleimide-based KLH conjugation offered the highest levels of anti-tumor immunity. Our data comparing sources of recombinant Id protein tumor antigens used in therapeutic cancer vaccines demonstrate that insect cell-derived antigens can offer several immunologic advantages over proteins derived from mammalian sources.


title: Identification of phosphorylation sites in the nucleocapsid protein (N protein) of SARS-coronavirus

text: After decoding the genome of SARS-coronavirus (SARS-CoV), next challenge is to understand how this virus causes the illness at molecular bases. Of the viral structural proteins, the N protein plays a pivot role in assembly process of viral particles as well as viral replication and transcription. The SARS-CoV N proteins expressed in the eukaryotes, such as yeast and HEK293 cells, appeared in the multiple spots on two-dimensional electrophoresis (2DE), whereas the proteins expressed in E. coli showed a single 2DE spot. These 2DE spots were further examined by Western blot and MALDI-TOF/TOF MS, and identified as the N proteins with differently apparent pI values and similar molecular mass of 50 kDa. In the light of the observations and other evidences, a hypothesis was postulated that the SARS-CoV N protein could be phosphorylated in eukaryotes. To locate the plausible regions of phosphorylation in the N protein, two truncated N proteins were generated in E. coli and treated with PKCα. The two truncated N proteins after incubation of PKCα exhibited the differently electrophoretic behaviors on 2DE, suggesting that the region of 1–256 aa in the N protein was the possible target for PKCα phosphorylation. Moreover, the SARS-CoV N protein expressed in yeast were partially digested with trypsin and carefully analyzed by MALDI-TOF/TOF MS. In contrast to the completely tryptic digestion, these partially digested fragments generated two new peptide mass signals with neutral loss, and MS/MS analysis revealed two phosphorylated peptides located at the “dense serine” island in the N protein with amino acid sequences, GFYAEGSRGGSQASSRSSSR and GNSGNSTPGSSRGNSPARMASGGGK. With the PKCα phosphorylation treatment and the partially tryptic digestion, the N protein expressed in E. coli released the same peptides as observed in yeast cells. Thus, this investigation provided the preliminary data to determine the phosphorylation sites in the SARS-CoV N protein, and partially clarified the argument regarding the phosphorylation possibility of the N protein during the infection process of SARS-CoV to human host.


title: Codes of Ethics in Public Health

text: This article is an updated version of the previous edition article by James C. Thomas, Ruth Gaare Bernheim, volume 1, pp. 754–759, © 2008, Elsevier Inc.


title: Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8(+) T Cells

text: Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority. CD8(+) Tissue-resident memory T (T(RM)) cells are a newly defined population that resides permanently in the nonlymphoid tissues including the lung. These cells are capable of providing local protection immediately after infection, thereby promoting rapid host recovery. Recent studies have offered new insights into the anatomical niches that harbor lung CD8(+) T(RM) cells, and also identified the requirement and limitations of T(RM) maintenance. However, it remains controversial whether lung CD8(+) T(RM) cells are continuously replenished by new cells from the circulation or permanently lodged in this site. A better understanding of how lung CD8(+) T(RM) cells are generated and maintained and the tissue-specific factors that drive local T(RM) formation is required for optimal vaccine development. This review focuses on recent advance in our understanding of CD8(+) T(RM) cell establishment and maintenance in the lung, and describes how those processes are uniquely regulated in this tissue.


Environment: Inhaling your food—and its cooking fuel


title: COVID-19 Immunity Certificates: Science, Ethics, Policy, and Law

text: There is much discussion of adopting COVID-19 immunity certificates to allow those proven to have antibodies to the SARS-CoV-2 virus that causes COVID-19 to resume normal life and help restart the economy. This article points out issues that must be considered before adopting any such program. These issues fall into six categories: the uncertain science of COVID-19 immunity; the questionable quality of COVID-19 antibody tests; practical problems with issuing such certificates; deciding how the certificates might be used; and ethical and social issues they would raise, especially fairness and self-infection; and potential legal barriers. It does not ultimately take a position on whether some narrow COVID-19 immunity plans should be adopted, concluding that the answer depends on too many currently unknown conditions. But it seventh part makes recommendations to decision-makers who might consider implementing such programs.


title: Mild course of Coronavirus disease 2019 and spontaneous severe acute respiratory syndrome coronavirus 2 clearance in a patient with depleted peripheral blood B‐cells due to treatment with rituximab

text: Over 4 million cases of Coronavirus disease 2019 (COVID‐19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been confirmed worldwide. Up to 20% of cases develop severe disease and the fatality rate are high.[1] Little is known however on the course of the infection in immunosuppressed patients. We therefore report the case of a patient with COVID‐19 under immunosuppression with rituximab. This 77‐year‐old woman was admitted to the hospital with a 5‐week history of unclear fever (up to 38.5°C), hypotension (80 mmHg systolic on self‐measurement), occasional mild shortness of breath and intermittent dry cough.


title: Implementation of an educational program for nursing students amidst the Ebola virus disease epidemic

text: Abstract Background The global Ebola virus disease (EVD) epidemic of 2014/2015 prompted faculty at Emory University to develop an educational program for nursing students to increase EVD knowledge and confidence and decrease concerns about exposure risk. Purpose The purpose of this article is to describe the development, implementation, and evaluation of the EVD Just-in-Time Teaching (JiTT) educational program. Methods Informational sessions, online course links, and a targeted, self-directed slide presentation were developed and implemented for the EVD educational program. Three student surveys administered at different time points were used to evaluate the program and change in students' EVD knowledge, confidence in knowledge, and risk concern. Discussion Implementation of a JiTT educational program effectively achieved our goals to increase EVD knowledge, decrease fear, and enhance student confidence in the ability to discuss EVD risk. These achievements were sustained over time. Conclusion JiTT methodology is an effective strategy for schools of nursing to respond quickly and comprehensively during an unanticipated infectious disease outbreak.


title: Studies on Mucosal Immunity Induced by Transmissible Gastroenteritis Virus Nucleocapsid Protein Recombinant Lactobacillus casei in Mice and Sow

text: Abstract Mucosal immunity plays an important role in protecting pigs against transmissible gastroenteritis virus (TGEV) infection. To elicit mucosal immune response against TGEV, we developed a surface antigen display system using the poly-[.gamma]-glutamate synthetase A (pgsA) protein of Bacillus subtilis as an anchoring matrix to express recombinant fusion proteins of pgsA and nucleocapsid protein of TGEV in Lactobacillus casei. Surface location of fusion protein was verified by ELISA and indirect immunofluorescence test. Oral and intranasal inoculations of pregnant sow and mice with recombinant L. casei resulted in high levels of serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) against recombinant N protein as demonstrated by ELISA. More importantly, the level of specific sIgA in colostrum significantly increased compared with that of IgG. The serum IgG levels of the piglets increased after suckling colostrum produced by sows was previously inoculated with recombinant L. casei. These results indicate that immunization with recombinant L. casei expressing TGEV N protein on its surface elicited high levels of specific sIgA and circulating IgG against TGEV N protein.


title: Lipid rafts play an important role in the early stage of severe acute respiratory syndrome-coronavirus life cycle

text: Abstract Lipid rafts are involved in the life cycle of many viruses. In this study, we showed that lipid rafts also play an important role in the life cycle of severe acute respiratory syndrome (SARS)-coronavirus (CoV). Cholesterol depletion by pretreatment of Vero E6 cells with methyl-β-cyclodextrin (MβCD) inhibited the production of SARS-CoV particles released from the infected cells. This inhibition was prevented by addition of cholesterol to the culture medium, indicating that the reduction of virus particle release was caused by the loss of cholesterol in the cell membrane. In contrast, cholesterol depletion at the post-entry stage (3h post-infection) caused only a limited effect on virus particle release. Northern blot analysis revealed that the levels of viral mRNAs were significantly affected by pretreatment with MβCD, but not by treatment at 3h post-infection. Interestingly, no apparent evidence for colocalization of angiotensin converting enzyme 2 with lipid rafts in the membrane of Vero E6 cells was obtained. These results suggest that lipid rafts could contribute to SARS-CoV infection in the early replication process in Vero E6 cells.


docid: gczgvipx

title: Understanding China’s growing involvement in global health and managing processes of change

text: BACKGROUND: Recent years have seen a rapid change in China’s global engagement and a recognition that solving global challenges will need to take the changing role of China into account. The paper discusses China’s growing involvement in global health. Health is an area where there is broad agreement over global priorities and, potentially, a fertile space to build new forms of collaboration that point the way towards the adaptation of global governance to a rapidly changing context. RESULTS: Drawing on previous analyses of China’s management of change in its domestic health reforms and interviews with a range of stakeholders in China, the UK and Switzerland, the paper argues that China’s engagement in global health is developing and diversifying rapidly in response to the central government’s desire to see a greater role for China in global health. This diversification is part of a pattern of change management familiar from China’s domestic reform experience. Explorations underway by a range of Chinese agencies form part of a process of rapid experimentation and experiential learning that are informing China’s search for (a) new global role(s). CONCLUSIONS: China is undergoing rapid institutional innovation and developing capacity for greater global engagement, including in health; however, substantial, recent leadership commitments make clear Chinese agencies’ need for continued exploration, innovation and rapid learning. How China engages globally is of significance to the world, not just China. The challenge for China, other global actors and multilateral organisations is to incorporate new approaches into existing global governance arrangements, including for the management of global health. This will require a willingness on all sides to learn from each other and invest the effort needed to build governance arrangements appropriate for the coming decades. This is not only important as a means of protecting global public health, but also as a demonstration of how governance arrangements can be adapted to the needs of a pluralistic global order in a context of rapid change.


title: Outcomes of severe human metapneumovirus-associated community-acquired pneumonia in adults

text: Abstract Background The outcomes of severe human metapneumovirus (HMPV)-associated pneumonia have not been adequately evaluated. Objectives We aimed to investigate the incidence and outcomes of severe HMPV-associated CAP and to compare them with those of severe IFV associated CAP. Study design From March 2010 to August 2017, all consecutive adult patients with severe HMPV-associated CAP and severe influenza virus (IFV)-associated CAP who required intensive care unit admission were prospectively identified and followed in a 2,700-bed tertiary care hospital. The characteristics and outcomes of severe HMPV-associated CAP patients were compared with those of severe IFV-associated CAP patients. Results HMPV and IFV were identified in 3.2% (50) and 7.0% (109) of the 1559 patients with severe CAP, respectively. The mortality rates were not significantly different between the HMPV and IFV groups (30-day mortality: 24.0% vs. 32.1%, p = 0.30; 60-day mortality: 32.0% vs. 38.5%, p = 0.43). Oral ribavirin therapy was not associated with improved outcome (60-day mortality: ribavirin therapy group 35.0% [7/20] vs. no ribavirin therapy group 30.0% [9/30], p = 0.71). Subgroup analyses showed no significant differences in mortality among non-immunocompromised (60-day mortality: HMPV 25.6% vs. IFV 31.1%, p = 0.55) and immunocompromised patients (60-day mortality; HMPV 54.5% vs. 54.3%, p = 0.99). The length of ICU and hospital stay did not differ between groups. Conclusions The incidence of HMPV infection was approximately half that of IFV infection in a cohort of patients with severe CAP. The mortality rate of severe HMPV-associated CAP was similar to that of severe IFV associated CAP.


title: The Global Emerging Infection Surveillance and Response System (GEIS), a U.S. government tool for improved global biosurveillance: a review of 2009

text: The Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) has the mission of performing surveillance for emerging infectious diseases that could affect the United States (U.S.) military. This mission is accomplished by orchestrating a global portfolio of surveillance projects, capacity-building efforts, outbreak investigations and training exercises. In 2009, this portfolio involved 39 funded partners, impacting 92 countries. This article discusses the current biosurveillance landscape, programmatic details of organization and implementation, and key contributions to force health protection and global public health in 2009.


title: The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages

text: BACKGROUND: Concurrent infection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is known as one of the major causes for porcine respiratory disease complex (PRDC). Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs) were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α) and FasL transcripts were determined, analyzed, and compared to prove the hypothesis. RESULTS: A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone. CONCLUSIONS: Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different inoculation orders of PCV2 and PRRSV in AMs leading to different results in viral antigen positivity, cytopathology, and cytokine profile may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions in PRDC exerted by dual infection with PCV2 and PRRSV and the variable clinical manifestations of PRDC-affected pigs in the field.


title: Chapter 25 Public Health Policies in European Union: An Innovation Strategy—Horizon 2020

text: Abstract Health planning and policy seek to create a group of mutually interacting bodies to produce goods and services to meet the health needs of a population. Recent developments in the health status of the population are characterized by continuous improvement in life expectancy, chronic diseases which absorb 90% of total health care expenditure, differences in the causes of mortality (more than 70% mortality from cancer, heart and brain, and external causes). The new trends in health indicators define the current health policies and lead to the necessity of adapting the health system so as to meet the changing health needs of the population. Especially in the context of the changes in the epidemiological spectrum and the variability in the indices of morbidity and mortality, the focus is not only to further prolong life expectancy but also to improve life expectancy without chronic diseases and without disabilities and to reduce the avoidable mortality, the potential years of life lost before the age of 65years. According to this approach, the main strategic priorities of health policy in the European Union for the period 2014–2020 are: (1) Prevention and health promotion (to combat diseases associated with the modern way of life), (2) Protection from cross-border threats (to address the external impact from cross-border relations, combating epidemics, pandemics), (3) Viability (to address the lack of resources by adopting innovation), (4) Accessibility (to assure the access to medical expertise).Therefore, the key priorities are the prevention of disease and the improvement of life in good health, the patient safety and quality of health services, and the readiness to manage crises and health risks.


Neurological disease associated with seasonal B19 virus infection in the United Kingdom


title: Quantitative Method for Comparative Assessment of Particle Removal Efficiency of Fabric Masks as Alternatives to Standard Surgical Masks for PPE

text: Summary In response to the COVID-19 pandemic, cloth masks are being used to control the spread of virus, but the efficacy of these loose-fitting masks is not well known. Here, tools and methods typically used to assess tight-fitting respirators were modified to quantify the efficacy of community- and commercially-produced fabric masks as PPE. Two particle counters concurrently sample ambient air and air inside the masks; mask performance is evaluated by mean particle removal efficiency and statistical variability when worn as designed and with a nylon overlayer, to independently assess fit and material. Worn as designed, both commercial surgical masks and cloth masks had widely varying effectiveness (53-75% and 28-90% particle removal efficiency, respectively). Most surgical-style masks improved with the nylon overlayer, indicating poor fit. This rapid testing method uses widely available hardware, requires only a few calculations from collected data, and provides both a holistic and aspect-wise evaluation of mask performance.


title: Importance of face masks for COVID-19 – a call for effective public education

text: Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the “dos-and-don’ts”.


title: Transmission routes of respiratory viruses among humans

text: Respiratory tract infections can be caused by a wide variety of viruses. Airborne transmission via droplets and aerosols enables some of these viruses to spread efficiently among humans, causing outbreaks that are difficult to control. Many outbreaks have been investigated retrospectively to study the possible routes of inter-human virus transmission. The results of these studies are often inconclusive and at the same time data from controlled experiments is sparse. Therefore, fundamental knowledge on transmission routes that could be used to improve intervention strategies is still missing. We here present an overview of the available data from experimental and observational studies on the transmission routes of respiratory viruses between humans, identify knowledge gaps, and discuss how the available knowledge is currently implemented in isolation guidelines in health care settings.


title: Ethical Perspectives on the Middle East Respiratory Syndrome Coronavirus Epidemic in Korea

text: Ethical considerations are essential in planning for and responding to outbreaks of infectious diseases. During the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Republic of Korea in 2015, serious challenges emerged regarding important ethical issues, such as transparency and the protection of privacy. The development of bioethics in Korea has been influenced by individualistic perspectives applied in clinical contexts, leading to a paucity of ethical perspectives relevant to population-level phenomena such as outbreaks. Alternative theories of public health ethics include the perspectives of relational autonomy and the patient as victim and vector. Public health actions need to incorporate clear and systematic procedures founded upon ethical principles. The MERS-CoV epidemic in Korea created significant public support for more aggressive early interventions in future outbreaks. This trend makes it all the more imperative for ethical principles and procedures to be implemented in future planning and responses to outbreaks in order to promote perceptions of legitimacy and civic participation.


title: Cultural orientation, power, belief in conspiracy theories, and intentions to reduce the spread of COVID‐19

text: The current study investigated cultural and psychological factors associated with intentions to reduce the spread of COVID‐19. Participants (n = 704) completed measures of individualism–collectivism, belief in conspiracy theories about COVID‐19, feelings of powerlessness, and intentions to engage in behaviours that reduce the spread of COVID‐19. Results revealed that vertical individualism negatively predicted intentions to engage in social distancing, directly and indirectly through both belief in COVID‐19 conspiracy theories and feelings of powerlessness. Vertical collectivism positively predicted social distancing intentions directly. Horizontal collectivism positively predicted social distancing intentions indirectly through feelings of powerlessness. Finally, horizontal collectivism positively predicted hygiene‐related intentions both directly and indirectly through lower feelings of powerlessness. These findings suggest that promoting collectivism may be a way to increase engagement with efforts to reduce the spread of COVID‐19. They also highlight the importance of examining the interplay between culture and both personal feelings (powerlessness) and information consumption (conspiracy theories) during times of crisis.


title: Infectivity of Severe Acute Respiratory Syndrome during Its Incubation Period

text: Objective To evaluate the infectivity of severe acute respiratory syndrome (SARS) during its incubation period by investigating chains of transmission and individuals isolated for medical observation with a view to providing scientific evidence for updating protocols of medical isolation. Methods Individuals related with the two SARS chains of transmission in Beijing in 2003 and a group of individuals isolated for medical observation in Haidian district of Beijing during the SARS outbreak were selected as subjects of study. Contactors with SARS patients and those with symptom development following the contacts were investigated via questionnaire. Serum samples were collected from super transmitters and tested for SARS-CoV antibody by neutralization test and enzyme linked immunosorbent assay (ELISA). Results A total of 1 112 contactors were investigated in three surveys. Of them, 669 had a history of close contact with symptomatic SARS patients, 101 developed symptoms with a rate of 15.1%, 363 had a history of close contact with patients in their incubation period, none of whom developed symptoms (0%). Serum samples were collected from 32 highly-exposed individuals, of whom 13 developing SARS symptoms after contact had serum samples positive for SARS-CoV antibody. Samples collected from the asymptomatic contactors were all negative for SARS-CoV antibody. Conclusion SARS cases are infectious only during their symptomatic period and are non-infectious during the incubation period. Isolation for medical observation should be placed for individuals who are in close contact with symptomatic SARS patients. The results of our study are of decisive significance for the Ministry of Health to the definition of SARS close contactor.


title: Bayesian mixture analysis for metagenomic community profiling

text: Deep sequencing of clinical samples is now an established tool for the detection of infectious pathogens, with direct medical applications. The large amount of data generated provides an opportunity to detect species even at very low levels, provided that computational tools can effectively interpret potentially complex metagenomic mixtures. Data interpretation is complicated by the fact that short sequencing reads can match multiple organisms and by the lack of completeness of existing databases, in particular for viral pathogens. This interpretation problem can be formulated statistically as a mixture model, where the species of origin of each read is missing, but the complete knowledge of all species present in the mixture helps with the individual reads assignment. Several analytical tools have been proposed to approximately solve this computational problem. Here, we show that the use of parallel Monte Carlo Markov chains (MCMC) for the exploration of the species space enables the identification of the set of species most likely to contribute to the mixture. The added accuracy comes at a cost of increased computation time. Our approach is useful for solving complex mixtures involving several related species. We designed our method specifically for the analysis of deep transcriptome sequencing datasets and with a particular focus on viral pathogen detection, but the principles are applicable more generally to all types of metagenomics mixtures. The work is implemented as a user friendly R package, available from CRAN: http://cran.r-project.org/web/packages/metaMix.


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title: APE1: A skilled nucleic acid surgeon

text: Abstract Before a deleterious DNA lesion can be replaced with its undamaged counterpart, the lesion must first be removed from the genome. This process of removing and replacing DNA lesions is accomplished by the careful coordination of several protein factors during DNA repair. One such factor is the multifunctional enzyme human apurinic/apyrimidinic endonuclease 1 (APE1), known best for its DNA backbone cleavage activity at AP sites during base excision repair (BER). APE1 preforms AP site incision with surgical precision and skill, by sculpting the DNA to place the cleavage site in an optimal position for nucleophilic attack within its compact protein active site. APE1, however, has demonstrated broad surgical expertise, and applies its DNA cleavage activity to a wide variety of DNA and RNA substrates. Here, we discuss what is known and unknown about APE1 cleavage mechanisms, focusing on structural and mechanistic considerations. Importantly, disruptions in the biological functions associated with APE1 are linked to numerous human maladies, including cancer and neurodegenerative diseases. The continued elucidation of APE1 mechanisms is required for rational drug design towards novel and strategic ways to target its associated repair pathways.


title: Reversible Cerebral Vasoconstriction Syndrome and Dissection in the Setting of COVID-19 Infection

text: The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.


title: Outbreaks of human coronavirus in a paediatric and neonatal intensive care unit

text: Human coronavirus 229E (HCoV) has been recently recognized as a potential agent of nosocomial viral respiratory infections (NRVI) in high-risk infants. We have confirmed this as fact through the study of a 1-year period of HCoV outbreaks occurring during a prospective survey of NRVI in a paediatric and neonatal intensive care unit (PNICU) using new molecular techniques for HCoV detection. Nasal samples obtained at admission and weekly thereafter for all hospitalised children, as well as monthly nasal samples from staff, were analysed using immunofluorescence for respiratory syncitial virus (RSV), influenza viruses A and B, paramyxoviruses 1, 2, 3 and adenoviruses. RT-PCR was used for HCoV detection. During the year 1998, 43 HCoV-related NRVI were detected in 152 neonates (incidence 28.3%), and 7 HCoV-related NRVI were found in 92 children (incidence 7.6%). Three HCoV-related outbreaks were observed (February, August and December), associated with a high prevalence of HCoV infection in the staff. During the August outbreak, 50% to 78% of hospitalised neonates and children were infected. Seventy-five percent of hospitalised preterm neonates with a gestational age less than 32 weeks and 52.4% of staff members were infected. Risk factors for NRVI in neonates were birth weight, gestational age, ventilation, oxygenation and hospitalisation length. Ninety-two percent of infected preterm neonates were symptomatic, mainly with bradycardia and respiratory worsening. These data provide additional evidence for a possibly significant role of HCoV in NRVI in a PNICU. The role of staff or hospitalised children in spreading HCoV is hypothesised.


title: A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

text: Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ring-shaped nanoparticles (N(SRS)) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with N(SRS) either intramuscularly, or both intramuscularly and intranasally using Montanide™ ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non-vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the non-vaccinated control calves. Thus N(SRS) vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction.


Developing Credible Knowledge during the COVID-19 Pandemic: Experiences with JACC Case Reports and the ACC COVID-19 Hub


Hallazgos cutáneos en la pandemia de COVID-19 en la Región de Murcia


title: Phylogeography of influenza A H5N1 clade 2.2.1.1 in Egypt

text: BACKGROUND: Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade 2.2.1.1, which has been found almost exclusively in Egypt. We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 2.2.1.1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin. RESULTS: Phylogeography models of hemagglutinin (HA) and neuraminidase (NA) suggest Ash Sharqiyah as the origin of virus spread, however the support is weak based on Kullback–Leibler values of 0.09 for HA and 0.01 for NA. Association Index (AI) values and Parsimony Scores (PS) were significant (p-value < 0.05), indicating that dispersion of H5N1 in Egypt was geographically structured. In addition, the Ash Sharqiyah to Al Gharbiyah and Al Fayyum to Al Qalyubiyah routes had the strongest statistical support. CONCLUSION: We found that the majority of routes with strong statistical support were in the heavily populated Delta region. In particular, the Al Qalyubiyah governorate appears to represent a popular location for virus transition as it represented a large portion of branches in both trees. However, there remains uncertainty about virus dispersion to and from this location and thus more research needs to be conducted in order to examine this. Phylogeography can highlight the drivers of H5N1 emergence and spread. This knowledge can be used to target public health efforts to reduce morbidity and mortality. For Egypt, future work should focus on using data about vaccination and live bird markets in phylogeography models to study their impact on H5N1 diffusion within the country.


title: Isolation, tissue distribution and molecular characterization of two recombinant canine coronavirus strains

text: Abstract Canine coronavirus (CCoV) is an enveloped RNA virus, responsible for gastrointestinal infection in dogs. To date, two different CCoV genotypes have been recognized, CCoV type I and CCoV type II. Recently, CCoV type II strains of potential recombinant origin with transmissible gastroenteritis virus (TGEV) were detected and characterized as a new subtype (CCoV-IIb) of canine coronavirus, in order to be differentiated from the “classical” CCoV type II strains (CCoV-IIa). In the present study, two CCoV-IIb strains were detected in the faeces and internal organs of two puppies, which died after presenting gastrointestinal symptoms. Mixed infection of both subtypes (CCoV-IIa/IIb) was detected in the faeces, while only CCoV-IIb was detected in the organs. Puppies were also infected by canine parvovirus type 2 (CPV-2). Both CCoV-IIb strains were isolated on cell cultures and subjected to sequence analysis and phylogeny. By means of RT-PCR and real time RT-PCR assays, tissue distribution and quantitation of viral loads took place. These cases represent the first description of tissue distribution and quantitation of CCoV-IIb strains, detected in the organs. The detection of CCoV-IIa strains, which is restricted to the faeces, suggests that CCoV-IIb strains may have an advantage in disseminating throughout a dog with CPV-2 coinfection, in contrast to common enteric CCoV-IIa strains.


title: Host Gene Expression of Macrophages in Response to Feline Coronavirus Infection

text: Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV.


title: Consumer behavior in confinement times: food choice and cooking attitudes in Spain

text: The present study provides an overview of the food related behavior of the Spanish population during the confinement period due to the Covid-19 sanitary emergency. A national survey was responded by 600 volunteers, who answered questions related to food consumption, home-food and cooking related habits (F&C), and the Spanish version of the Dutch Eating Behavior Questionnaire. In general, most consumers could be considered “External eaters”; F&C questionnaire allowed segmenting the population in “low-cooking engagement”, “health -concerned” and “health-disregarded” groups. These consumers’ segments reported different behavior, highlighting, for example, the increase of snacks and ultra-processed food consumption of the health-disregarded group.


title: Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses

text: Influenza virus research has recently undergone a shift from a virus-centric perspective to one that embraces the full spectrum of virus-host interactions and cellular signaling events that determine disease outcome. This change has been brought about by the increasing use and expanding scope of high-throughput molecular profiling and computational biology, which together fuel discovery in systems biology. In this review, we show how these approaches have revealed an uncontrolled inflammatory response as a contributor to the extreme virulence of the 1918 pandemic and avian H5N1 viruses, and how this response differs from that induced by the 2009 H1N1 viruses responsible for the most recent influenza pandemic. We also discuss how new animal models, such as the Collaborative Cross mouse systems genetics platform, are key to the necessary systematic investigation of the impact of host genetics on infection outcome, how genome-wide RNAi screens have identified hundreds of cellular factors involved in viral replication, and how systems biology approaches are making possible the rational design of new drugs and vaccines against an ever-evolving respiratory virus.


docid: ylsgzhdj

title: Metagenomic water quality monitoring with a portable laboratory

text: We describe the technical feasibility of metagenomic water quality analysis using only portable equipment, for example mini-vacuum pumps and filtration units, mini-centrifuges, mini-PCR machines and the memory-stick sized MinION of Oxford Nanopore Technologies, for the library preparation and sequencing of 16S rRNA gene amplicons. Using this portable toolbox on site, we successfully characterized the microbiome of water samples collected from Birtley Sewage Treatment Plant, UK, and its environs. We also demonstrated the applicability of the portable metagenomics toolbox in a low-income country by surveying water samples from the Akaki River around Addis Ababa, Ethiopia. The 16S rRNA sequencing workflow, including DNA extraction, PCR amplification, sequencing library preparation, and sequencing was accomplished within one working day. The metagenomic data became available within 24–72 h, depending on internet speed. Metagenomic analysis clearly distinguished the microbiome of pristine samples from sewage influenced water samples. Metagenomic analysis identified the potential role of two bacterial genera not conventionally monitored, Arcobacter and Aeromonas, as predominant faecal pollution indicators/waterborne hazards. Subsequent quantitative PCR analysis validated the high Arcobacter butzleri abundances observed in the urban influenced Akaki River water samples by portable next generation sequencing with the MinION device. Overall, our field deployable metagenomics toolbox advances the capability of scientists to comprehensively monitor microbiomes anywhere in the world, including in the water, food and drinks industries, the health services, agriculture and beyond.


title: NIH Disease Funding Levels and Burden of Disease

text: BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.


title: Recomendaciones éticas para la toma de decisiones difíciles en las unidades de cuidados intensivos ante la situación excepcional de crisis por la pandemia por covid-19: revisión rápida y consenso de expertos

text: Abstract In view of the exceptional public health situation caused by the COVID-19 pandemic, a consensus work has been promoted from the ethics group of the Spanish Society of the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC), with the objective of finding some answers from ethics to the crossroads between the increase of people with intensive care needs and the effective availability of means. In a very short period, the medical practice framework has been changed to a "catastrophe medicine" scenario, with the consequent change in the decision-making parameters. In this context, the allocation of resources or the prioritization of treatment become crucial elements, and it is important to have an ethical reference framework to be able to make the necessary clinical decisions.For this, a process of narrative review of the evidence has been carried out, followed by u. Unsystematic consensus of experts, which has resulted in both the publication of a position paper and recommendations from SEMICYUC itself, and the consensus between 18 scientific societies and 5 institutes / chairs of bioethics and palliative care of a framework document of reference for general ethical recommendations in this context of crisis.


COVID‐19 and Immigrants’ Access to Sexual and Reproductive Health Services in the United States


title: COVID-19 identification in chest X-ray images on flat and hierarchical classification scenarios

text: Abstract Background and Objective:The COVID-19 can cause severe pneumonia and is estimated to have a high impact on the healthcare system. Early diagnosis is crucial for correct treatment in order to possibly reduce the stress in the healthcare system. The standard image diagnosis tests for pneumonia are chest X-ray (CXR) and computed tomography (CT) scan. Although CT scan is the gold standard, CXR are still useful because it is cheaper, faster and more widespread. This study aims to identify pneumonia caused by COVID-19 from other types and also healthy lungs using only CXR images. Methods:In order to achieve the objectives, we have proposed a classification schema considering the following perspectives: i) a multi-class classification; ii) hierarchical classification, since pneumonia can be structured as a hierarchy. Given the natural data imbalance in this domain, we also proposed the use of resampling algorithms in the schema in order to re-balance the classes distribution. We observed that, texture is one of the main visual attributes of CXR images, our classification schema extract features using some well-known texture descriptors and also using a pre-trained CNN model. We also explored early and late fusion techniques in the schema in order to leverage the strength of multiple texture descriptors and base classifiers at once. To evaluate the approach, we composed a database, named RYDLS-20, containing CXR images of pneumonia caused by different pathogens as well as CXR images of healthy lungs. The classes distribution follows a real-world scenario in which some pathogens are more common than others. Results:The proposed approach tested in RYDLS-20 achieved a macro-avg F1-Score of 0.65 using a multi-class approach and a F1-Score of 0.89 for the COVID-19 identification in the hierarchical classification scenario. Conclusions:As far as we know, the top identification rate obtained in this paper is the best nominal rate obtained for COVID-19 identification in an unbalanced environment with more than three classes. We must also highlight the novel proposed hierarchical classification approach for this task, which considers the types of pneumonia caused by the different pathogens and lead us to the best COVID-19 recognition rate obtained here.


Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein


HEALTH STATUS OF LIVER TRANSPLANTED PATIENTS DURING THE CORONAVIRUS OUTBREAK IN ITALY: A LARGE SINGLE CENTER EXPERIENCE FROM MILAN


How Community and Unity Can Help Americans Survive


title: 8 Modification of textile surfaces using nanoparticles

text: Abstract: The application of nanotechnology on textile materials could lead to the addition of several functional properties to the base substrate. Those functional properties are of the highest importance, giving noticeable improvements in the wear comfort and care. This chapter discusses various functional properties – for example, anti-microbial, easy-care, ultraviolet-protecting and flame-retardant finishes that could be achieved by the application of metal and metal oxide nanoparticles. In addition, novel applications of textile materials using nanotechnology in biological detection, decomposition of toxic gases, self-decontamination and military protection gear are discussed.


title: Global Health and Foreign Policy

text: Health has long been intertwined with the foreign policies of states. In recent years, however, global health issues have risen to the highest levels of international politics and have become accepted as legitimate issues in foreign policy. This elevated political priority is in many ways a welcome development for proponents of global health, and it has resulted in increased funding for and attention to select global health issues. However, there has been less examination of the tensions that characterize the relationship between global health and foreign policy and of the potential effects of linking global health efforts with the foreign-policy interests of states. In this paper, the authors review the relationship between global health and foreign policy by examining the roles of health across 4 major components of foreign policy: aid, trade, diplomacy, and national security. For each of these aspects of foreign policy, the authors review current and historical issues and discuss how foreign-policy interests have aided or impeded global health efforts. The increasing relevance of global health to foreign policy holds both opportunities and dangers for global efforts to improve health.


Communicable Disease and Health Protection Quarterly Review: July to September 2003


title: E-mail-based symptomatic surveillance combined with self-collection of nasal swabs: a new tool for acute respiratory infection epidemiology

text: Summary Objective We examined the feasibility of combining communication by e-mail and self-collection of nasal swabs for the prospective detection of acute respiratory infections in a non-medical setting. Methods The study was conducted among a convenience sample of employees (n =53) at a research institution (December 2009–April 2010). Real-time data on the occurrence of acute respiratory symptoms and a nasal self-swab were collected prospectively, with automated weekly e-mails as a reminder mechanism. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect respiratory viral pathogens in the swabs. Results Fifty-one out of 53 participants completed the study. The study design was well accepted. Thirty (∼57%) participants reported at least one episode of acute respiratory infection and returned the nasal swab during the study period (eight participants reported two episodes). The majority had no difficulties taking the self-swab and preferred this to swabbing by study personnel. Most participants obtained and returned the swabs within the recommended time. Viral respiratory pathogens were detected in 19 of 38 swabs (50%), with coronaviruses 229E/NL63 and OC43 and rhinoviruses A and B constituting 17 positive swabs (89%). Conclusions Combining e-mail-based symptomatic surveillance with nasal self-swabbing promises to be a powerful tool for the real-time identification of incident cases of acute respiratory infections and the associated pathogens in population-based studies.


title: Isolation and characterization of Acanthamoeba spp. from air-conditioners in Kuala Lumpur, Malaysia

text: Abstract During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At genotypic characterization, these isolates were placed into T3 (IMU14); T5 (IMU16 and IMU17) and T4 (all the remaining isolates). To predict the potential pathogenicity of these Acanthamoeba isolates, thermo- and osmotolerance tests were employed; many isolates were predicted as potential human pathogens based on the outcome of these tests. This is the first time potentially pathogenic Acanthamoeba have been isolated from air-conditioners in Malaysia.


The Impact of the COVID-19 Pandemic on Parkinson’s Disease: Hidden Sorrows and Emerging Opportunities


The Early Impact of COVID-19 Pandemic on Surgical Urologic Oncology Practice in Turkey: Multi-Institutional Experience from Different Geographic Areas


Encephalitis Associated with COVID-19 Infection in an 11 Year-Old Child


title: Amplification refractory mutation system PCR assays for the detection of variola and Orthopoxvirus

text: Abstract PCR assays that can identify the presence of variola virus (VARV) sequences in an unknown DNA sample were developed using principles established for the amplification refractory mutation system (ARMS). The assay’s specificity utilised unique single nucleotide polymorphisms (SNP) identified among Orthopoxvirus (OPV) orthologs of the vaccinia virus Copenhagen strain A13L and A36R genes. When a variola virus specific primer was used with a consensus primer in an ARMS assay with different Orthopoxvirus genomes, a PCR product was only amplified from variola virus DNA. Incorporating a second consensus primer into the assay produced a multiplex PCR that provided Orthopoxvirus generic and variola-specific products with variola virus DNA. We tested two single nucleotide polymorphisms with a panel of 43 variola virus strains, collected over 40 years from countries across the world, and have shown that they provide reliable markers for variola virus identification. The variola virus specific primers did not produce amplicons with either assay format when tested with 50 other Orthopoxvirus DNA samples. Our analysis shows that these two polymorphisms were conserved in variola virus genomes and provide a reliable signature of Orthopoxvirus species identification.


title: Neuroinvasive and Neurotropic Human Respiratory Coronaviruses: Potential Neurovirulent Agents in Humans

text: In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Several recognized respiratory viral agents have a neuroinvasive capacity since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Among the various respiratory viruses, coronaviruses are important pathogens of humans and animals. Human Coronaviruses (HCoV) usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly, and immune-compromised individuals, they can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome, or even severe acute respiratory syndrome (SARS). The respiratory involvement of HCoV has been clearly established since the 1960s. In addition, for almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic and could induce an overactivation of the immune system, in part by participating in the activation of autoreactive immune cells that could be associated with autoimmunity in susceptible individuals. Furthermore, it was shown that in the murine CNS, neurons are the main target of infection, which causes these essential cells to undergo degeneration and eventually die by some form of programmed cell death after virus infection. Moreover, it appears that the viral surface glycoprotein (S) represents an important factor in the neurodegenerative process. Given all these properties, it has been suggested that these recognized human respiratory pathogens could be associated with the triggering or the exacerbation of neurological diseases for which the etiology remains unknown or poorly understood.


title: The Role of Autophagy in Eosinophilic Airway Inflammation

text: Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.


title: Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability

text: Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.


title: Efficient oligonucleotide probe selection for pan-genomic tiling arrays

text: BACKGROUND: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. RESULTS: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. CONCLUSION: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.


title: COVID-19 created chaos across the globe: Three novel quarantine epidemic models

text: The latest version of human coronavirus said to be COVID-19 came out as a sudden pandemic disease within human population and in the absence of vaccination and proper treatment till date, it daunting threats heavily to human lives, infecting more than 12, 11, 214 people and death more than 67, 666 people in 208 countries across the globe as on April 06, 2020, which is highly alarming. When no treatment or vaccine is available till date and to avoid COVID-19 to be transmitted in the community, social distancing is the only way to prevent the disease, which is well taken into account in our novel epidemic models as a special compartment, that is, home isolation. Based on the transmitting behaviour of COVID-19 in the human population, we develop three quarantine models of this pandemic taking into account the compartments: susceptible population, immigrant population, home isolation population, infectious population, hospital quarantine population, and recovered population. Local and global asymptotic stability is proved for all the three models. Extensive numerical simulations are performed to establish the analytical results with suitable examples. Our research reveals that home isolation and quarantine to hospitals are the two pivot force-control policies under the present situation when no treatment is available for this pandemic.


title: Challenges and opportunities for surveillance data to inform public health policy on chronic non-communicable diseases: Canadian perspectives

text: Summary A number of major challenges face surveillance systems in the field of chronic disease. The complex interplay of risk factors and determinants that result in chronic disease is calling into question traditional surveillance systems in terms of what is collected to inform policy decisions. At the same time, the complexity presents an opportunity to broaden the evidence base on which arguments can be based for chronic disease intervention to increase their potential to influence policy makers. This article describes some initiatives in Canada to enhance the capacity and utility of surveillance systems and their associated data to inform policy making in the field of chronic disease.


title: Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na(+)/K(+)-ATPase independent proteolysis

text: An unprecedented biological function of natural cardenolides independent of their membrane target Na(+)/K(+)-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na(+)/K(+)-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na(+)/K(+)-ATPase α1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Herein, we further explored a Na(+)/K(+)-ATPase-independent signaling axis induced by natural cardenolides that also afforded significant anti-coronaviral activity for porcine TGEV and human HCoV-OC43. Using pharmacological inhibition and gene silencing techniques, we found that this anti-TGEV or anti-HCoV-OC43 activity was caused by JAK1 proteolysis and mediated through upstream activation of Ndfip1/2 and its effector NEDD4. This study provides novel insights into the pharmacological effects of natural cardenolides, and is expected to inform their future development as antiviral agents.


title: Tempol ameliorates murine viral encephalomyelitis by preserving the blood–brain barrier, reducing viral load, and lessening inflammation

text: Abstract Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating disease of the human central nervous system (CNS). Most of the knowledge about the pathogenesis of MS has been derived from murine models, such as experimental autoimmune encephalomyelitis and viral encephalomyelitis. Here, we infected female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV-59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing encephalomyelitis. In untreated animals, neurological symptoms developed quickly: 90% of infected mice died 10 days after virus inoculation and the few survivors presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses on the first day and daily doses for 7 days plus 2 mM tempol in the drinking water ad libitum) profoundly altered the disease outcome: neurological symptoms were attenuated, mouse survival increased up to 70%, and half of the survivors behaved as normal mice. Not surprisingly, tempol substantially preserved the integrity of the CNS, including the blood–brain barrier. Furthermore, treatment with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration, and levels of markers of inflammation, such as expression of inducible nitric oxide synthase, transcription of tumor necrosis factor-α and interferon-γ, and protein nitration. The results indicate that tempol ameliorates murine viral encephalomyelitis by altering the redox status of the infectious environment that contributes to an attenuated CNS inflammatory response. Overall, our study supports the development of therapeutic strategies based on nitroxides to manage neuroinflammatory diseases, including MS.


title: Farm characteristics and calf management practices on dairy farms with and without diarrhea: A case-control study to investigate risk factors for calf diarrhea

text: Abstract Calf diarrhea is one of the most important problems in calf rearing on dairy farms worldwide. Besides pathogens, several noninfectious management factors, especially management around birth, colostrum management, calf housing, feeding, and hygiene are important in the pathogenesis of diarrhea. To date, few data are available concerning calf rearing management on small and medium-sized dairy farms that are typical for Austria and the alpine region. Consequently, the objectives of this case-control study were to evaluate routine calf management practices on Austrian dairy farms and to examine differences in management between farms with and without the presence of calf diarrhea to identify risk factors. Overall, 100 dairy farms were visited. Of these farms, 50 were chosen based on the history and presence of calf diarrhea (case farms). Another 50 farms with no presence of calf diarrhea were chosen to serve as a standard of comparison (control farms). On farms, management was evaluated by face-to-face interview, and health status and hygiene were surveyed. Several calf rearing management procedures were similar on all of the visited farms, especially in areas regulated by national and European law. These factors include colostrum management and feeding. Consequently, no influence of these factors on the appearance of calf diarrhea could be detected. In contrast, other areas such as hygiene measures differed between farms and showed a partial association with the presence of calf diarrhea on farm. Variables related to diarrhea on farm were farm size; that is, the number of cows on farm. Farms with diarrhea cases were larger (median 40 cows, interquartile range 24.5 to 64.0) compared with farms with no presence of diarrhea (median 28 cows, interquartile range 18.8 to 44.0). Other risk factors that influenced the presence of diarrhea were the presence of other farm animal species on the farm [odds ratio (OR) 26.89, 95% confidence interval (CI): 2.64 to 273.5], frequency of cleaning of the calving area (OR 0.12, 95% CI: 0.02 to 0.79), the placement of individual calf housings (barn vs. outdoors; OR 0.02, 95% CI: 0.00 to 0.47), and the presence of respiratory tract disease (OR 52.49, 95% CI: 1.26 to 2,181.83). The possible influence of these factors on the appearance of calf diarrhea should be considered when farmers are advised.


docid: agurctan

title: Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

text: Hepatitis B virus (HBV) is regarded as a stealth virus, invading and replicating efficiently in human liver undetected by host innate antiviral immunity. Here, we show that type I interferon (IFN) induction but not its downstream signaling is blocked by HBV replication in HepG2.2.15 cells. This effect may be partially due to HBV X protein (HBx), which impairs IFNβ promoter activation by both Sendai virus (SeV) and components implicated in signaling by viral sensors. As a deubiquitinating enzyme (DUB), HBx cleaves Lys63-linked polyubiquitin chains from many proteins except TANK-binding kinase 1 (TBK1). It binds and deconjugates retinoic acid-inducible gene I (RIG I) and TNF receptor-associated factor 3 (TRAF3), causing their dissociation from the downstream adaptor CARDIF or TBK1 kinase. In addition to RIG I and TRAF3, HBx also interacts with CARDIF, TRIF, NEMO, TBK1, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon (IKKi) and interferon regulatory factor 3 (IRF3). Our data indicate that multiple points of signaling pathways can be targeted by HBx to negatively regulate production of type I IFN. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13238-010-0141-8 and is accessible for authorized users.


title: Viral etiology of influenza‐like illnesses during the influenza season between December 2011 and April 2012

text: The aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in Turkish children during the 2011–2012 influenza season. Nasal swabs were obtained from patients with symptoms suggestive of an influenza‐like illness between December 2011 and April 2012. Samples were analyzed with multiplex real‐time polymerase chain reaction (RT‐PCR) to help identify the causative viral pathogen. A total of 200 patients were enrolled in the study. A respiratory virus was detected successfully in 102 (51%) children; influenza A (H3N2) in 39.2%, influenza B in 23.5%, RSV in 15.6%, rhinovirus in 13.7%, bocavirus in 2.9%, coronavirus in 2.9%, and metapneumovirus in 0.9% of patients. Only one patient was co‐infected with bocavirus and influenza A virus. A statistically significant difference in the mean age of presentation was observed between the various viral pathogens (P < 0.001). Patients with RSV were significantly younger whereas children infected with the influenza viruses were significantly older. Comparison of symptoms revealed that fever and headache occurred more frequently with the influenza viruses than the other viruses combined (P < 0.001, <0.05). Durations of symptoms such as fever, cough, nasal congestion, and rhinorrhea were also significantly longer in the influenza group (P < 0.001, <0.005, <0.001, <0.005, respectively). Demographic analyses revealed that the school/daycare attendance was the only parameter associated with a significantly increased risk for influenza infection. With an overall viral pathogen detection rate of 51%, findings of the present study suggest other respiratory pathogens, whether viral or bacterial, may also lead to hospital visits due to influenza‐like illnesses in children. J. Med. Virol. 86:865–871, 2014. © 2013 Wiley Periodicals, Inc.


Surgeon’s protection during ophthalmic surgery in the Covid-19 era: a novel fitted drape for ophthalmic operating microscopes


N95 respirator, COVID‐19, and health care worker


Preventing and Controlling Measures of 2019 Coronavirus Disease (COVID-19) : Practice in Psychogeriatric Ward


title: Development of Pediatric Surgical Decision-Making Guidelines for COVID-19 in a New York City Children's Hospital

text: Abstract Objective During the COVID-19 pandemic, experience-based guidelines are needed in the pediatric population in order to deliver high quality care in a new way that keeps patients and healthcare workers safe and maximizes hospital resource utilization. Background The COVID-19 pandemic has created an unprecedented strain on national health care resources, particularly in New York City, the epicenter of the outbreak in the United States. Prudent allocation of surgical resources during the pandemic quickly became essential, and there is an unprecedented need to weigh the risks of operating versus delaying intervention in our pediatric patients. Methods Here we describe our experience in surgical decision-making during the COVID-19 pandemic in the pediatric surgical population at Morgan Stanley Children’s Hospital of New York-Presbyterian (MSCHONY), which has served as a major urban catchment area for COVID-19 positive pediatric patients. We describe how we have adjusted our current treatment of multiple facets of pediatric surgery including oncology, trauma, minimally invasive procedures, and extracorporeal membrane oxygenation (ECMO). Conclusions Our pediatric surgery department had to creatively and expeditiously adjust our protocols, guidelines, and workforce to not only serve our pediatric population but merge ourselves with our adult hospital system during the COVID pandemic. Type of Study Clinical Research Paper Level of Evidence Level V


title: Sequence and organization of barley yellow dwarf virus genomic RNA.

text: The nucleotide sequence of the genomic RNA of barley yellow dwarf virus, PAV serotype was determined, except for the 5'-terminal base, and its genome organization deduced. The 5,677 nucleotide genome contains five large open reading frames (ORFs). The genes for the coat protein (1) and the putative viral RNA-dependent RNA polymerase were identified. The latter shows a striking degree of similarity to that of carnation mottle virus (CarMV). By comparison with corona- and retrovirus RNAs, it is proposed that a translational frameshift is involved in expression of the polymerase. An ORF encoding an Mr 49,797 protein (50K ORF) may be translated by in-frame readthrough of the coat protein stop codon. The coat protein, an overlapping 17K ORF, and a 3'6.7K ORF are likely to be expressed via subgenomic mRNAs.


title: Chapter 25 Chiroptera

text: Abstract With over 1200 species identified, bats represent almost one quarter of the world’s mammals. Bats provide crucial environmental services, such as insect control and pollination, and inhabit a wide variety of ecological niches on all continents except Antarctica. Despite their ubiquity and ecological importance, relatively little has been published on diseases of bats, while much has been written on bats’ role as reservoirs in disease transmission. This chapter will focus on diseases and pathologic processes most commonly reported in captive and free-ranging bats. Unique anatomical and histological features and common infectious and non-infectious diseases will be discussed. As recognition of both the importance and vulnerability of bats grows, particularly following population declines in North America due to the introduction of the fungal disease white-nose syndrome, efforts should be made to better understand threats to the health of this unique group of mammals.


title: Representations of SARS in the British newspapers

text: In the Spring of 2003, there was a huge interest in the global news media following the emergence of a new infectious disease: severe acute respiratory syndrome (SARS). This study examines how this novel disease threat was depicted in the UK newspapers, using social representations theory and in particular existing work on social representations of HIV/AIDS and Ebola to analyse the meanings of the epidemic. It investigates the way that SARS was presented as a dangerous threat to the UK public, whilst almost immediately the threat was said to be ‘contained’ using the mechanism of ‘othering’: SARS was said to be unlikely to personally affect the UK reader because the Chinese were so different to ‘us’; so ‘other’. In this sense, the SARS scare, despite the remarkable speed with which it was played out in the modern global news media, resonates with the meanings attributed to other epidemics of infectious diseases throughout history. Yet this study also highlights a number of differences in the social representations of SARS compared with earlier epidemics. In particular, this study examines the phenomena of ‘emerging and re-emerging infectious diseases’ over the past 30 or so years and suggests that these have impacted on the faith once widely held that Western biomedicine could ‘conquer’ infectious disease.


title: RNA: interactions drive functionalities

text: RNA is produced from the majority of human genomic sequences, although only a relatively small portion of these transcripts has known functions. Diverse RNA species interact with RNA, DNA, proteins, lipids, and metabolites to form intricate molecular networks. In this review, we attempt to delineate diverse RNA functions by interaction types between RNA and other macromolecules. Through such interactions RNAs participate in essentially every major molecular function and process, including information flow and storage, environment sensing, signal transduction, and gene regulation at transcriptional and posttranscriptional levels. Through such interactions, RNAs promote or inhibit diverse biological processes, and act as catalyzer or quencher to modulate the pace of these progresses. Alterations and personal variations of these interactions are mechanistically coupled with disease etiology and phenotypical variations for clinical use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-019-05230-7) contains supplementary material, which is available to authorized users.


title: The Asia Pacific Academic Consortium for Global Public Health and Medicine: Stabilizing South-South Academic Collaboration

text: Developmental strategies over the last 4 decades have generally tended to transfer knowledge and technology along north–south axes as trickle-down theories in development, especially in health knowledge transfers, prevailed. Limited efforts in development assistance for health (DAH) were made to promote south-south cooperation for basic health needs. Globalization with increased educational networks and development health assistance has enhanced the potential for more effective south-south partnerships for health. The stages of development in a consortium and key catalysts in the metamorphosis to a south-south partnership are identified: leadership, resources, expertise, visibility participation, and dynamism of a critical mass of young professionals.


title: Identification of peptide domains involved in the subcellular localization of the feline coronavirus 3b protein

text: Feline coronavirus (FCoV) has been identified as the aetiological agent of feline infectious peritonitis (FIP), a highly fatal systemic disease in cats. FCoV open reading frame 3 (ORF3) encodes accessory proteins 3a, 3b and 3 c. The FCoV 3b accessory protein consists of 72 amino acid residues and localizes to nucleoli and mitochondria. The present work focused on peptide domains within FCoV 3b that drive its intracellular trafficking. Transfection of different cell types with FCoV 3b fused to enhanced green fluorescent protein (EGFP) or 3×FLAG confirmed localization of FCoV 3b in the mitochondria and nucleoli. Using serial truncated mutants, we showed that nucleolar accumulation is controlled by a joint nucleolar and nuclear localization signal (NoLS/NLS) in which the identified overlapping pat4 motifs (residues 53–57) play a critical role. Mutational analysis also revealed that mitochondrial translocation is mediated by N-terminal residues 10–35, in which a Tom20 recognition motif (residues 13–17) and two other overlapping hexamers (residues 24–30) associated with mitochondrial targeting were identified. In addition, a second Tom20 recognition motif was identified further downstream (residues 61–65), although the mitochondrial translocation evoked by these residues seemed less efficient as a diffuse cytoplasmic distribution was also observed. Assessing the spatiotemporal distribution of FCoV 3b did not provide convincing evidence of dynamic shuttling behaviour between the nucleoli and the mitochondria.


title: Co-lethality studied as an asset against viral drug escape: the HIV protease case

text: BACKGROUND: Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL) or a co-lethal. Like invariant positions, SL sets (SL linked couples) are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic) lethality. RESULTS: From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap), 4 (in the cantilever) and 5 (in the fulcrum) amino acid positions were found. CONCLUSIONS: These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. REVIEWERS: This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.