title: Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19

text: BACKGROUND: Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. METHOD: In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. RESULTS: A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. CONCLUSIONS: Although randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.


title: Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors

text: Summary Background Studies on the fusion-inhibitory peptides derived from the heptad repeat 1 and 2 (HR1 and HR2) regions of the HIV-1 envelope glycoprotein gp41 provided crucial information on the viral fusogenic mechanism. We used a similar approach to study the fusogenic mechanism of severe-acute-respiratory-syndrome-associated coronavirus (SARS-CoV). Methods We tested the inhibitory activity against infection of two sets of peptides corresponding to sequences of SARS-CoV spike protein HR1 and HR2 regions and investigated the interactions between the HR1 and HR2 peptides by surface plasmon resonance, sedimentation equilibration analysis, circular dichroism, native polyacrylamide-gel electrophoresis, size exclusion high-performance liquid chromatography, and computer-aided homology modelling and molecule docking analysis. Findings One peptide, CP-1, derived from the HR2 region, inhibited SARS-CoV infection in the micromolar range. CP-1 bound with high affinity to a peptide from the HR1 region, NP-1. CP-1 alone had low -helicity and self-associated to form a trimer in phosphate buffer (pH 7·2). CP-1 and NP-1 mixed in equimolar concentrations formed a six-helix bundle, similar to the fusogenic core structure of HIV-1 gp41. Interpretation After binding to the target cell, the transmembrane spike protein might change conformation by association between the HR1 and HR2 regions to form an oligomeric structure, leading to fusion between the viral and target-cell membranes. At the prefusion intermediate state, CP-1 could bind to the HR1 region and interfere with the conformational changes, resulting in inhibition of SARS-CoV fusion with the target cells. CP-1 might be modifiable to increase its anti-SARS-CoV activity and could be further developed as an antiviral agent for treatment or prophylaxis of SARS-CoV infection.


title: Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection

text: Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype often cause severe pneumonia and multiple organ failure in humans, with reported case fatality rates of more than 60%. To develop a clinical antibody therapy, we generated a human-mouse chimeric monoclonal antibody (MAb) ch61 that showed strong neutralizing activity against H5N1 HPAI viruses isolated from humans and evaluated its protective potential in mouse and nonhuman primate models of H5N1 HPAI virus infections. Passive immunization with MAb ch61 one day before or after challenge with a lethal dose of the virus completely protected mice, and partial protection was achieved when mice were treated 3 days after the challenge. In a cynomolgus macaque model, reduced viral loads and partial protection against lethal infection were observed in macaques treated with MAb ch61 intravenously one and three days after challenge. Protective effects were also noted in macaques under immunosuppression. Though mutant viruses escaping from neutralization by MAb ch61 were recovered from macaques treated with this MAb alone, combined treatment with MAb ch61 and peramivir reduced the emergence of escape mutants. Our results indicate that antibody therapy might be beneficial in reducing viral loads and delaying disease progression during H5N1 HPAI virus infection in clinical cases and combined treatment with other antiviral compounds should improve the protective effects of antibody therapy against H5N1 HPAI virus infection.


title: COVID-19 revisiting inflammatory pathways of arthritis

text: Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1β or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19.


title: Bioaerosol sampling: sampling mechanisms, bioefficiency and field studies

text: Summary Investigations into the suspected airborne transmission of pathogens in healthcare environments have posed a challenge to researchers for more than a century. With each pathogen demonstrating a unique response to environmental conditions and the mechanical stresses it experiences, the choice of sampling device is not obvious. Our aim was to review bioaerosol sampling, sampling equipment, and methodology. A comprehensive literature search was performed, using electronic databases to retrieve English language papers on bioaerosol sampling. The review describes the mechanisms of popular bioaerosol sampling devices such as impingers, cyclones, impactors, and filters, explaining both their strengths and weaknesses, and the consequences for microbial bioefficiency. Numerous successful studies are described that point to best practice in bioaerosol sampling, from the use of small personal samplers to monitor workers' pathogen exposure through to large static samplers collecting airborne microbes in various healthcare settings. Of primary importance is the requirement that studies should commence by determining the bioefficiency of the chosen sampler and the pathogen under investigation within laboratory conditions. From such foundations, sampling for bioaerosol material in the complexity of the field holds greater certainty of successful capture of low-concentration airborne pathogens. From the laboratory to use in the field, this review enables the investigator to make informed decisions about the choice of bioaerosol sampler and its application.


title: Cytokine and nitric oxide patterns in dogs immunized with LBSap vaccine, before and after experimental challenge with Leishmania chagasi plus saliva of Lutzomyia longipalpis

text: Abstract In the studies presented here, dogs were vaccinated against Leishmania (Leishmania) chagasi challenge infection using a preparation of Leishmania braziliensis promastigote proteins and saponin as adjuvant (LBSap). Vaccination with LBSap induced a prominent type 1 immune response that was characterized by increased levels of interleukin (IL-) 12 and interferon gamma (IFN-γ) production by peripheral blood mononuclear cells (PBMC) upon stimulation with soluble vaccine antigen. Importantly, results showed that this type of responsiveness was sustained after challenge infection; at day 90 and 885 after L. chagasi challenge infection, PBMCs from LBSap vaccinated dogs produced more IL-12, IFN-γ and concomitant nitric oxide (NO) when stimulated with Leishmania antigens as compared to PBMCs from respective control groups (saponin, LB- treated, or non-treated control dogs). Moreover, transforming growth factor (TGF)-β decreased in the supernatant of SLcA-stimulated PBMCs in the LBSap group at 90 days. Bone marrow parasitological analysis revealed decreased frequency of parasitism in the presence of vaccine antigen. It is concluded that vaccination of dogs with LBSap vaccine induced a long-lasting type 1 immune response against L. chagasi challenge infection.


title: COVID-19 outbreak and cancer radiotherapy disruption in italy: Survey endorsed by the italian association of radiotherapy and clinical oncology (AIRO)

text: Italy experienced one of the world’s deadliest COVID-19 outbreaks and healthcare systems had to instantly reorganise activity. The Italian Radiation Oncology Departments adapted numerous solutions to minimize the disruptions. Information technologies, treatment prioritization and implementation of hypofractionation and protection procedures allowed balancing between cancer patient care and patient/healthcare workers safety.


title: Association between continuity of care and emergency department visits and hospitalization in senior adults with asthma-COPD overlap

text: Abstract Objective To investigate associations between continuity of care (COC) and emergency department (ED) visits and hospitalization for chronic obstructive pulmonary disease (COPD) or asthma among elderly adults with asthma-COPD overlap (ACO). Methods A retrospective cohort study was performed using the Taiwan National Health Insurance research database. A total of 1141 ACO patients aged ≥65 years during 2005–2011 were observed and followed for 2 years. The Bice and Boxerman COC index (COCI) was used to evaluate COC by considering ambulatory care visits duo to COPD or asthma in the first year; ED visits and hospitalization for COPD or asthma were identified in the subsequent year, respectively. The COCI was divided into three levels (COCI < 0.3= low, 0.3 ≤ COCI<1=medium, COCI = 1=high). The Cox model was used to estimate the hazard ratio (HR) for ED visits and hospital admissions due to COPD or asthma. Results The average COCI was 0.55. 21.3% patients received outpatient care from a single physician. Compared to patients with high COC, those with low and medium COC had a higher risk of ED visits (aHR = 2.80 and 2.69, P < .01) and admissions (aHR = 1.80 and 1.72, P < .05). Conclusion Increasing COC is beneficial for elderly patients with ACO in disease management. Policymakers could create effective pay-for-performance programs for the elderly ACO population to enhance COC and improve care outcomes.


title: Organoids as a Powerful Model for Respiratory Diseases

text: Insults to the alveoli usually lead to inefficient gas exchange or even respiratory failure, which is difficult to model in animal studies. Over the past decade, stem cell-derived self-organizing three-dimensional organoids have emerged as a new avenue to recapitulate respiratory diseases in a dish. Alveolar organoids have improved our understanding of the mechanisms underlying tissue homeostasis and pathological alterations in alveoli. From this perspective, we review the state-of-the-art technology on establishing alveolar organoids from endogenous lung epithelial stem/progenitor cells or pluripotent stem cells, as well as the use of alveolar organoids for the study of respiratory diseases, including idiopathic pulmonary fibrosis, tuberculosis infection, and respiratory virus infection. We also discuss challenges that need to be overcome for future application of alveolar organoids in individualized medicine.


COVID-19 and the Bioeconomy


Managing change in the urology department of a large hospital in Italy during the COVID‐19 pandemic


title: Deploying Biomolecules as Anti-COVID-19 Agents

text: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) known as COVID-19 has emerged as a major threat to human existence. COVID-19 seems to have undergone adaptive evolution through an intermediate host, most likely bats. The flu leads to severe pneumonia that causes respiratory and multi-organ failure. The absence of any known treatment procedures, drugs, or vaccines has created panic around the World. The need is to develop rapid testing kits, drugs and vaccines. However, these proposals are time-consuming processes. At present social distancing along with previously known traditional medicines can act as quick and short-term alternatives for treating this viral flu.


docid: bzazdxuo

title: Registered Reports offer recognition for rigour

text: Nature Communications are pleased to announce that we are now considering Registered Reports for publication in the fields of cognitive neuroscience, human behaviour and psychology, as well as epidemiology.


Physical distancing amidst social connectivity: time to re-visit ‘social distancing’ as India fights COVID-19


title: Detection of new biallelic polymorphisms in the human MxA gene

text: The interferon-inducible human MxA protein plays an important role in innate defense against an array of viruses. One might expect allelic diversity at the MxA locus to influence the timing and magnitude of its expression or even the range of viruses whose biological cycle is inhibited by the encoded product. Here we have collected 267 samples of genomic DNA from three distinct populations (European, Asian, and African) and have systematically sequenced the promoter of the MxA gene and its 17 exons in order to inventory its allelic variants. Eighteen single-nucleotide polymorphisms were detected, four of which had never been identified before. Two of these, located in the promoter (at positions −309 and −101 respectively), might affect the MxA expression pattern. The other two result in substitutions (Gly255Glu and Val268Met) in the protein’s N-terminal region that might directly affect its antiviral function. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11033-012-1708-7) contains supplementary material, which is available to authorized users.


title: Would it be legally justified to impose vaccination in Israel? Examining the issue in light of the 2013 detection of polio in Israeli sewage

text: BACKGROUND: The detection of wild poliovirus in Israeli sewage in May 2013 led the health authorities to decide that children who had been vaccinated with IPV would also be vaccinated with OPV. The decision sought to protect vulnerable Israeli individuals who were either not vaccinated with IPV or who suffered from an immune deficiency, to preserve Israel’s status as a polio-free country, to prevent the virus’ “exportation” into vulnerable polio-free countries, and to participate in the global efforts toward the eradication of polio. After a massive public persuasion campaign, 79% of the children born after 2004 were vaccinated as well as 69% of the children residing in central Israel. A 2014 State Comptroller Report stated that the Ministry of Health should draw conclusions from the low compliance rates in certain Israeli regions. GOALS: The article seeks to examine the legal legitimacy of mandatory vaccination in the service of eradicating a contagious disease (as opposed to preventing a pandemic outbreak), which was one of the objectives in the 2013 Polio case. It more specifically relates to current Israeli law as well as to a hypothetical new public health law which would authorize health officials to oblige vaccination and enforce this through the use of criminal sanctions. METHOD: Qualitative content analysis through the interpretation of court judgements, laws, legislative protocols, health ministry guidelines and documented discussions of the Advisory Committee on Infectious Diseases and Immunization. MAIN FINDINGS AND CONCLUSION: A mandatory vaccination backed by criminal sanctions in the service of the eradication of contagious diseases would probably be perceived as infringing on the constitutional right to autonomy to a greater extent than necessary according to Israeli law and case law precedents. There may be some added value inherent in a new public health law which would authorize health officials to oblige vaccination where nonrestrictive measures have been ineffective. However, the law should also specify a variety of sanctions to accompany the enforcement of mandatory vaccinations which would be formulated from least to most restrictive according to the “intervention ladder” concept. The law should also describe the circumstances which would justify the implementation of each and every sanction as well as the procedural safeguards designed for established decisions and fairness toward the individual(s) whose rights are infringed by the application of these sanctions.


docid: wvxohfum

title: Theoretical and applied study of the psychological and educational effects of lockdown in primary school students in Argentina

text: Abstract Emotions are complex states, which have a fundamental role for children’s mental health and learning. The proper self-regulation of emotions allows to tolerate frustrations, improves social skills and healthy bonds with peers and adults in the environment (Bisquerra, 2003, p. 12). The lack of regulation causes discomfort that leads to a decrease in academic performance (Graziano, Reavis, Keanes & Calkins, 2006) and particularly in reading comprehension, because this competence requires motivation and cognitive processes that will allow to process the linguistic code, interpret it and represent it symbolically (Alonso-Tapia, 2005, p. 64). In this work, we show the essential relationship between emotional regulation and reading comprehension in primary school students. After that, we study the effect of lockdown on these two processes. The aim is to have preliminary information about the challenges and effects of the current situation. To do this, a semi-structured survey has been conducted of parents and teachers in order to assess the psychological and educational effects of the current health situation. The results of 40 semi-structured telephone surveys are analyzed, 20 of parents of children with learning disorders and 20 of their classroom teachers in Traslasierra, Córdoba-Argentina. The results inform that the students and their parents have difficulties to regulate their emotions and this emotional struggle has a negative impact on comprehension of texts. The problems that previously presented in these two areas have increased due to the lack of adaptation of activities by teachers, the lack of knowledge of their parents to help them and the difficulty in accessing digital technologies. Both parents and teachers express that lockdown affects learning processes, although parents are also concerned about the effects on social life.


title: Surveillance and control of infectious diseases at local, national and international levels

text: ABSTRACT New emerging and re-emerging threats, the weight of public opinion and new technology for surveillance and treatment are likely to impact on how, and if, effective surveillance can be performed in the future. If surveillance fails to address the needs of practitioners and policy-makers, it is likely that there will be loss of confidence. Current surveillance systems are reasonably effective at detecting significant events that are localised in time and space. It is more difficult to detect diffuse and progressive events with a slow increase over time or sporadic and widespread events without obvious links to time, place or person. Detection of these events relies on good data collection, comparative background data and sophisticated analytical tools. To improve surveillance systems, we need methods with the appropriate sensitivity and specificity for the outputs desired. Targeted surveillance should enable better ascertainment of those cases which must be considered and those which can be dismissed. New methods, such as mathematical modelling and geographical information systems, support conventional surveillance in moving events into the known and predictable category. It is important to integrate surveillance across local, regional and international levels and to base surveillance on local public health structures. The purpose and value of data aggregation at each level and the amount of detail needed at each level must be carefully evaluated. The key to all these improvements is developing the workforce. Surveillance needs individuals with a broad range of skills: clinical, epidemiological, anthropological, and mathematical; in particular, people who can think laterally. These individuals must be encouraged through effective training courses, good mentorship, networking and clear career structures.


title: Antiviral effect of Chinese herbal prescription JieZe-1 on adhesion and penetration of VK2/E6E7 with herpes simplex viruses type 2

text: Abstract Ethnopharmacological relevance The Chinese Herbal Prescription JieZe-1(JZ-1), added and subtracted from Yihuang Decoction, a famous formula in the 12th year of Kangxi in Qing Dynasty, has a clear effect on Genital Herpes (GH) and no obvious adverse reactions occur clinically. JZ-1 also has preventive and therapeutic effects on Trichomonas vaginitis, Candida albicans vaginitis and GH in vitro and in vivo experiments. Aim of study The effect and mechanism of JZ-1 on anti-herpes simplex virus type 2(HSV-2) in vitro focusing on adhesion and penetration stages were investigated. Materials and methods A model of HSV-2 infection of VK2/E6E7 was developed. In order to explore JZ-1's anti-HSV-2 effect in vitro, cell morphology, ultrastructural pathology, cell viability and expression of viral glycoprotein D (gD) were assessed at 6 h, 12 h, 18 h, and 24 h of JZ-1 treatment. Then we measured the exact time required for adhesion and penetration of HSV-2 into VK2/E6E7 among a series of times at room temperature and under temperature control techniques. We treated VK2/E6E7 with JZ-1, penciclovir, or berberine and explored the mechanism of JZ-1 in blocking HSV-2 adhesion and penetration of host cells by assessing the cell ultrastructural pathology, viability, viral proteins gB, gD, VP16, ICP5, and ICP4 and host cell proteins HVEM, Nectin-1, and Nectin-2. Results HSV-2 can fully adhere and penetrate into VK/E6E7 within 5 mins at room temperature while it takes 60mins under temperature control techniques. JZ-1 and penciclovir showed significant anti-HSV-2 effects, with improved host cell morphologies and increased host cell viabilities observed after treatment for 24 h. The anti-HSV-2 effect of JZ-1 can be detected after treatment for 6 h while that of penciclovir was not obvious until treatment for 12 h. JZ-1 showed distinct effect on HSV-2 adhesion and penetration stages by significantly reducing the expression of viral proteins gB, gD, VP16, ICP5, and ICP4, improving cell morphology and increasing cell viability. However, these effects were not exerted via downregulated expression of membrane fusion-related proteins such as HVEM, Nectin-1, or Nectin-2. The specific anti-HSV-2 mechanism of JZ-1 need to be further explored. Conclusion The anti-HSV-2 effect of JZ-1 was superior to that of penciclovir and berberine in vitro, and was mainly mediated by enhancing host cell defense and blocking adhesion and penetration of HSV-2.


title: COVID‐19: Legal implications for critical care

text: The COVID‐19 pandemic has caused an unprecedented challenge for the provision of critical care. Anticipating an unsustainable burden on the health service, the UK government introduced numerous legislative measures culminating in the Coronavirus Act, which interfere with existing legislation and rights. However, the existing standards and legal frameworks relevant to critical care clinicians are not extinguished but anticipated to adapt to a new context. This new context influences the standard of care that can be reasonably provided and yields numerous human rights considerations, for example in the use of restraints or the restrictions placed upon patients and visitors under the Infection Prevention and Control guidance. The changing landscape, has also highlighted previously unrecognised legal dilemmas. The perceived difficulties in the provision of PPE for employees pose a legal risk for trusts and a regulatory risk for clinicians. The spectre of rationing critical care poses a number of legal issues. Notably, the flux between clinical decisions based on best interests towards decisions explicitly based on resource considerations should be underpinned by an authoritative public policy decision to preserve legitimacy and lawfulness. Such a policy should be medically coherent, legally robust and ethically justified. The current crisis yields numerous challenges for clinicians aspiring to remain faithful to medico‐legal and human rights principles developed over many decades, especially when such considerations could easily be dismissed. However, it is exactly at such times that these principles are needed the most and clinicians play a disproportionate role in safeguarding such principles for the most vulnerable.


title: IgY: A promising antibody for use in immunodiagnostic and in immunotherapy

text: Abstract Immunoglobulin IgY is the major antibody produced by chickens (Gallus domesticus). After their V-C gene is rearranged in B cells, IgY is continually synthesized, excreted into the blood and transferred to the egg yolk, where it is accumulated. IgY is produced by hens to provide their offspring with an effective humoral immunity against the commonest avian pathogens until full maturation of their own immune system. In this review we aim to give an overview about the generation, structure, properties of IgY, as well as the advantages of chicken antibodies use over mammalian antibodies in immunodiagnostics and immunotherapy.


title: Bismuth Complexes Inhibit the SARS Coronavirus

text: Festgehalten: Bismutkomplexe, darunter Ranitidinbismutcitrat, inhibieren die Nucleosidtriphosphat‐Hydrolase‐ und DNA‐Entfaltungsaktivitäten der SARS‐Coronavirus(SCV)‐Helicase effektiv und reduzieren das Ausmaß der SCV‐Replikation in infizierten Zellen erheblich. Es lohnt sich also, Wirkstoffe auf Bismutbasis für die Behandlung von SCV‐Infektionen in vivo weiter zu untersuchen. ss=Einzelstrang‐DNA, ds=Doppelstrang‐DNA.[Image: see text]


title: Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states

text: BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus). METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration. RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State. CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3326-0) contains supplementary material, which is available to authorized users.


A more detailed picture of the epidemiology of Middle East respiratory syndrome coronavirus


title: CDC Support for Global Public Health Emergency Management

text: Recent pandemics and rapidly spreading outbreaks of infectious diseases have illustrated the interconnectedness of the world and the importance of improving the international community’s ability to effectively respond. The Centers for Disease Control and Prevention (CDC), building on a strong foundation of lessons learned through previous emergencies, international recognition, and human and technical expertise, has aspired to support nations around the world to strengthen their public health emergency management (PHEM) capacity. PHEM principles streamline coordination and collaboration in responding to infectious disease outbreaks, which align with the core capacities outlined in the International Health Regulations 2005. CDC supports PHEM by providing in-country technical assistance, aiding the development of plans and procedures, and providing fellowship opportunities for public health emergency managers. To this end, CDC partners with US agencies, international partners, and multilateral organizations to support nations around the world to reduce illness and death from outbreaks of infectious diseases.


title: Applications of genetic engineering in veterinary medicine

text: Abstract A mutation of just one gene will cause abnormal cell behavior leading to the synthesis of a dysfunctional protein. This mutation will inevitably result in the cell functioning only marginally or not at all. Other genetic mutations interfere with the cell’s normal life cycle, especially the cell-division cycle. The goal behind recombinant DNA technology is to deliver the correct version of a mutated gene to the cell so that the expression will lead to the normal production of protein and the restoration of normal cell function. This can be considered qualitatively different from other conventional treatments due to genetic material being a putative therapeutic agent. By altering the genetic material of cells, gene therapy may correct, or one day cure, the specific disease pathophysiology. Genetic engineering has been used in veterinary medicine to diagnose, prevent and treat diseases, breed different species and produce transgenic animals for therapeutic proteins or xenografting. In this review the current status of recombinant DNA technology and its application in veterinary medicine together with the obstacles to, and applications of, genetic engineering in veterinary medicine are discussed.


title: The Network of Interactions Among Porcine Reproductive and Respiratory Syndrome Virus Non-structural Proteins

text: The RNA synthesis of porcine reproductive and respiratory syndrome virus (PRRSV), a positive-strand RNA virus, is compartmentalized in virus-induced double-membrane vesicles where viral proteins and some cellular proteins assemble into replication and transcription complexes (RTCs). The viral replicase proteins are the major components of the RTCs but the physical associations among these non-structural proteins (nsps) remain elusive. In this study, we investigated the potential interactions between PRRSV nsps by yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC) and pull-down assays. Our analyses revealed a complex network of interactions involving most of PRRSV nsps. Among them, nsp9 and nsp12 were identified as the hubs of the nsp interactome; transmembrane proteins nsp2 and nsp5 both interacted with nsp3, indicating that the three membrane-bound proteins might bind together to form the scaffold to support the association of RTCs with the intracellular membrane. The PRRSV nsp interactions identified in this study may provide valuable clues for future researches on the RTC formation and function.


title: Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children

text: BACKGROUND/AIMS: Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections. METHODS: A total of 183 and 236 hospitalized children with acute encephalitis-like syndrome and respiratory tract infection, respectively, were screened for anti-CoV IgM antibodies. The expression profiles of multiple cytokines were determined in CoV-positive patients. RESULTS: Anti-CoV IgM antibodies were detected in 22/183 (12.02%) and 26/236 (11.02%) patients with acute encephalitis-like syndrome and respiratory tract infection, respectively. Cytokine analysis revealed that the level of serum granulocyte colony-stimulating factor (G-CSF) was significantly higher in both CoV-CNS and CoV-respiratory tract infection compared with healthy controls. Additionally, the serum level of granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly higher in CoV-CNS infection than in CoV-respiratory tract infection. In patients with CoV-CNS infection, the levels of IL-6, IL-8, MCP-1, and GM-CSF were significantly higher in their cerebrospinal fluid samples than in matched serum samples. CONCLUSION: To the best of our knowledge, this is the first report showing a high incidence of CoV infection in hospitalized children, especially with CNS illness. The characteristic cytokine expression profiles in CoV infection indicate the importance of host immune response in disease progression.


title: Imaging features and evolution on CT in 100 COVID-19 pneumonia patients in Wuhan, China

text: OBJECTIVES: To investigate CT images of 100 confirmed COVID-19 pneumonia patients to describe the lesion distribution, CT signs, and evolution during different courses. METHODS: A retrospective study of 100 COVID-19 pneumonia patients without ARDS was performed, and CT scans were reviewed. A COVID-19 pneumonia course diagram was drawn. Mann-Whitney U test was used to compare the lesion distribution and CT scores, χ(2) test was used to compare the CT findings between different stages. RESULTS: A total of 272 CT scans from 100 patients (mean age, 52.3 years ± 13.1) were investigated. Four patients with lung abnormalities on CT first showed negative RT-PCR result and turned positive afterwards. One hundred sixty-nine (62.1%) showed predominantly peripheral distribution. The CT scores of the upper zone (3.4 ± 3.6) were significantly lower than those of the middle (5.0 ± 3.9) and lower (4.8 ± 3.6) zones (p < 0.001). The CT scores of the anterior zones (4.9 ± 4.7) were significantly lower than those of the posterior zones (8.4 ± 6.2) (p < 0.001). In the early rapid progressive stage (1~7 days), ground glass opacity (GGO) plus reticular pattern (58.1%), GGO plus consolidation (43.0%), and GGO (41.9%) were all common. In the advanced stage (8~14 days), GGO plus consolidation (79.8%) and repairing CT signs (subpleural line, bronchus distortion, and fibrotic strips) showed a significant increase (p < 0.05). In the absorption stage, GGO plus consolidation (9.1%) sharply decreased (p < 0.05). CONCLUSION: CT imaging of COVID-19 pneumonia showed a predominantly peripheral, middle and lower, and posterior distribution. The early rapid progressive stage is 1~7 days from symptom onset, the advanced stage with peak levels of abnormalities on CT is 8~14 days, and the abnormalities started to improve after 14 days. KEY POINTS: • The course of COVID-19 pneumonia consists of three stages: 1~7 days is the early rapid progressive stage, 8~14 days is the advanced stage, and after 14 days, the abnormalities started to decrease. • In the early rapid progressive stage, GGO plus a reticular pattern, GGO plus consolidation, and GGO were all common signs; in the advanced stage, signs of progression and absorption coexisted; lung abnormalities showed an asynchronous process with parts with absorption and parts progressing. • Lung abnormalities mainly showed predominantly peripheral, middle, and lower distribution.


title: Expert recommendations on blood purification treatment protocol for patients with severe COVID-19 Recommendation and consensus

text: Abstract Coronavirus disease (COVID-19) was first diagnosed in Wuhan in December 2019. The World Health Organization defined the subsequent outbreak of COVID-19 worldwide as a public health emergency of international concern. Epidemiological data indicate that at least 20% of COVID-19 patients have severe disease. In addition to impairment of the respiratory system, acute kidney injury (AKI) is a major complication. Immune damage mediated by cytokine storms and concomitant AKI is a key factor for poor prognosis. Based on previous experience of blood purification for patients with severe acute respiratory syndrome and Middle East respiratory syndrome combined with clinical front-line practice, we developed a blood purification protocol for patients with severe COVID-19. This protocol is divided into four major steps. The first step is to assess whether patients with severe COVID-19 require blood purification. The second step is to prescribe a blood purification treatment for patients with COVID-19. The third step is to monitor and adjust parameters of blood purification. The fourth step is to evaluate the timing of discontinuation of blood purification. It is expected that blood purification will play a key role in effectively reducing the mortality of patients with severe COVID-19 through the standardized implementation of the present protocol.


title: To compare the incomparable: COVID-19 pneumonia and high-altitude disease

text: COVID-19 pneumonia is a viral infection; high-altitude pulmonary oedema is a non-cardiogenic oedema. Some clinicians have found the clinical features similar. It is important to clarify such misconceptions to prevent erroneous treatment strategies https://bit.ly/2KOBi3F


title: Adopting PROs in virtual and outpatient management of RA

text: The COVID-19 pandemic has catalysed the sudden adoption of telemedicine in the management of rheumatic diseases. In this abrupt transition from in-person visits to telemedicine, can patient-reported outcomes (PROs) help ensure that we continue to achieve optimum disease control and address the concerns of people living with rheumatoid arthritis?


A47 Origin and possible genetic recombination of the middle east respiratory syndrome coronavirus from the first imported case in china: phylogenetics and coalescence analysis


title: Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion

text: The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.


title: SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii

text: Abstract Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1–4) and 5 were evaluated for SARS-CoV 3CLpro inhibitory activities and showed potent inhibitory activities with IC50 values of 10.3, 5.5, 9.9, and 2.6μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 =21.7μM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1–4 have proven to be competitive by the kinetic analysis.


title: SARS and Pregnancy: A Case Report

text: We report a laboratory-confirmed case of severe acute respiratory syndrome (SARS) in a pregnant woman. Although the patient had respiratory failure, a healthy infant was subsequently delivered, and the mother is now well. There was no evidence of viral shedding at delivery. Antibodies to SARS virus were detected in cord blood and breast milk.


title: Impact of porcine group A rotavirus co-infection on porcine epidemic diarrhea virus pathogenicity in piglets

text: Abstract Porcine epidemic diarrhea virus (PEDV) and porcine group A rotavirus (PGAR) are the main causative agents of acute diarrhea in piglets. In South Korea, PGAR is prevalent in piglets naturally infected with PEDV. Piglets naturally co-infected with PEDV and PGAR appeared to have severe and prolonged diarrhea that was distinct from that commonly observed. The aim of this study was to determine the impact of PGAR co-infection on PEDV pathogenicity in piglets. Thirty-six colostrum-deprived, one-day old, Large White-Duroc crossbred pigs were randomly divided into four equal groups: PEDV, PEDV/PGAR, PGAR, and control groups. The piglets were euthanized at 1, 2, or 3 days post-inoculation (DPI) to measure the villous height:crypt depth (VH:CD) ratio and to collect fecal samples for RT-PCR and virus isolation. No significant differences in mean VH:CD ratio and clinical symptoms (diarrhea, vomiting, dehydration, and anorexia) were observed between the PEDV/PGAR-infected and PEDV-infected groups of piglets at 1, 2 and 3 DPI; however, at 2 and 3 DPI, PGAR was detected in all fecal samples by RT-PCR and virus isolation. These findings failed to detect any interaction between PEDV and porcine rotavirus in the small intestines of piglets, suggesting that concurrent infection of PGAR may not synergistically enhance intestinal villous atrophy of piglets with PEDV disease. We propose that the severe diarrhea exhibited in PEDV and PGAR co-infected piglets may be more associated with the immunity level of the host rather than to any synergistic effect of PGAR on PEDV enteritis.


Inhibitors of the Renin–Angiotensin–Aldosterone System and Covid-19


title: The State of the Science of health care epidemiology, infection control, and patient safety, 2004

text: Being aware and implementing the latest and best scientific evidence in infection control and health care epidemiology is critical to enhancing patient outcomes. In this review, the latest published scientific data in health care epidemiology and patient safety were reviewed for the period May 2003-May 2004. Medline reviews and reviews of infection control and infectious diseases journals were used for this period. The latest guidelines and publications on antimicrobial resistance, nursing or infection control professional staffing, West Nile virus, and Severe Acute Respiratory Syndrome (SARS) are included. Awareness of these and other important infection control publications is essential if the latest measures are to be implemented to prevent and control health care-associated infections.


title: Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses

text: Abstract The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).


title: Designing and building oncolytic viruses

text: Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost the killing of uninfected cancer cells. The goal of the field is to develop OVs that are easily manufactured, efficiently delivered to disseminated sites of cancer growth, undergo rapid intratumoral spread, selectively kill tumor cells, cause no collateral damage and pose no risk of transmission in the population. Here we discuss the many virus engineering strategies that are being pursued to optimize delivery, intratumoral spread and safety of OVs derived from different virus families. With continued progress, OVs have the potential to transform the paradigm of cancer care.


title: B-cell activation in cats with feline infectious peritonitis (FIP) by FIP-virus-induced B-cell differentiation/survival factors

text: It has been suggested that antibody overproduction plays a role in the pathogenesis of feline infectious peritonitis (FIP). However, only a few studies on the B-cell activation mechanism after FIP virus (FIPV) infection have been reported. The present study shows that: (1) the ratio of peripheral blood sIg(+) CD21(−) B-cells was higher in cats with FIP than in SPF cats, (2) the albumin-to-globulin ratio has negative correlation with the ratio of peripheral blood sIg(+) CD21(−) B-cell, (3) cells strongly expressing mRNA of the plasma cell master gene, B-lymphocyte-induced maturation protein 1 (Blimp-1), were increased in peripheral blood in cats with FIP, (4) mRNA expression of B-cell differentiation/survival factors, IL-6, CD40 ligand, and B-cell-activating factor belonging to the tumor necrosis factor family (BAFF), was enhanced in macrophages in cats with FIP, and (5) mRNAs of these B-cell differentiation/survival factors were overexpressed in antibody-dependent enhancement (ADE)-induced macrophages. These data suggest that virus-infected macrophages overproduce B-cell differentiation/survival factors, and these factors act on B-cells and promote B-cell differentiation into plasma cells in FIPV-infected cats.


title: The Mechanics of Translocation: A Molecular “Spring-and-Ratchet” System

text: The translation of genetic information into proteins is a fundamental process of life. Stepwise addition of amino acids to the growing polypeptide chain requires the coordinated movement of mRNA and tRNAs through the ribosome, a process known as translocation. Here, we review current understanding of the kinetics and mechanics of translocation, with particular emphasis on the structure of a functional mammalian ribosome stalled during translocation by an mRNA pseudoknot. In the context of a pseudoknot-stalled complex, the translocase EF-2 is seen to compress a hybrid-state tRNA into a strained conformation. We propose that this strain energy helps overcome the kinetic barrier to translocation and drives tRNA into the P-site, with EF-2 biasing this relaxation in one direction. The tRNA can thus be considered a molecular spring and EF-2 a Brownian ratchet in a “spring-and-ratchet” system within the translocation process.


title: Refined compartmental models, asymptomatic carriers and COVID-19

text: The goal of this article is to analyze some compartmental models specially designed to model the spread of a disease whose transmission has the same features as COVID-19. The major contributions of this article are: (1) Rigorously find sufficient conditions for the outbreak to only have one peak, i.e. for no second wave of infection to form; (2) Investigate the formation of other waves of infection when such conditions are not met; (3) Use numerical simulations to analyze the different roles asymptomatic carriers can have. We also argue that dividing the population into non-interacting groups leads to an effective reduction of the transmission rates. As in any compartmental model, the goal of this article is to provide qualitative understanding rather than exact quantitative predictions.


Effects of COVID-19 pandemic in the field of orthopaedics


title: Risk-adapted Treatment Strategy For COVID-19 Patients

text: BACKGROUND: There are no clear expert consensus or guidelines on how to treat 2019 coronavirus disease (COVID-19). The objective of this study is to investigate the short-term effect of risk-adapted treatment strategy on patients with COVID-19. METHODS: We collected the medical records of 55 COVID-19 patients for analysis. We divided these patients into mild, moderate and severe groups, and risk-adapted treatment approaches were given according to the illness severity. RESULTS: Twelve patients were in mild group and 22 were in moderate group (non-severe group, n = 34), and 21 patients were in severe group. At the end of the first two weeks after admission, clinical manifestations had completely despeared in 31(91.2%)patients in non-severe group, and 18(85.7%) patients in severe group (p = 0.85). Both groups had a satisfied chest CT imaging recovery, which includes 22(64.7%) patients in non-severe group and 12(57.1%) patients in severe group recovered at least 50% of the whole leisions in the first week, and 28(82.4%) and 16(76.2%) recovered at least 75% in the second week, respectively. There were no significant differences in SARS-CoV-2 nucleic acid negativity (p = 0.92). There were also no significant differences in the levels of SARS-CoV-2-IgM and IgG antibody production between the two groups (p = 0.13, 0.62). There were 45 cases were discharged from the hospital, and no patients died at the time of this clinical analysis. CONCLUSIONS: Risk-adapted treatment strategy was associated with significant clinical manifestations alleviation and clinical imaging recovery. In severe COVID-19 patients, early and short-term use of low-dose methylprednisolone was beneficial and did not delay SARS-CoV-2 nucleic acid clearance and influence IgG antibody production.


title: Evaluation of NxTAG Respiratory Pathogen Panel and Comparison with xTAG Respiratory Viral Panel Fast v2 and Film Array Respiratory Panel for Detecting Respiratory Pathogens in Nasopharyngeal Aspirates and Swine/Avian-Origin Influenza A Subtypes in Culture Isolates

text: This study evaluated a new multiplex kit, Luminex NxTAG Respiratory Pathogen Panel, for respiratory pathogens and compared it with xTAG RVP Fast v2 and FilmArray Respiratory Panel using nasopharyngeal aspirate specimens and culture isolates of different swine/avian-origin influenza A subtypes (H2N2, H5N1, H7N9, H5N6, and H9N2). NxTAG RPP gave sensitivity of 95.2%, specificity of 99.6%, PPV of 93.5%, and NPV of 99.7%. NxTAG RPP, xTAG RVP, and FilmArray RP had highly concordant performance among each other for the detection of respiratory pathogens. The mean analytic sensitivity (TCID50/ml) of NxTAG RPP, xTAG RVP, and FilmArray RP for detection of swine/avian-origin influenza A subtype isolates was 0.7, 41.8, and 0.8, respectively. All three multiplex assays correctly typed and genotyped the influenza viruses, except for NxTAG RRP that could not distinguish H3N2 from H3N2v. Further investigation should be performed if H3N2v is suspected to be the cause of disease. Sensitive and specific laboratory diagnosis of all influenza A viruses subtypes is especially essential in certain epidemic regions, such as Southeast Asia. The results of this study should help clinical laboratory professionals to be aware of the different performances of commercially available molecular multiplex RT-PCR assays that are commonly adopted in many clinical diagnostic laboratories.


title: Framing the structure of global open innovation research

text: Abstract This study proposes a way of mapping open innovation research structure by quantitatively analyzing open innovation research papers retrieved from Web of Science database. A total of 130 papers are retrieved in this study and 62 papers which contain keywords are chosen for research structure visualization. Open innovation research networks are quantitatively investigated by combining network theory and keyword co-occurrence. Contour maps of open innovation are also created on the basis of networks for visualization. The networks and contour maps can be expressed differently by choosing different information as the main actors, such as the paper author, the institute, the country or the author-keywords, to reflect open innovation research structures in micro, meso, and macro-levels, respectively. The quantitative ways of exploring open innovation research structure are investigated to unveil important or emerging open innovation components as well as to demonstrate visualization of the structure of global open innovation research. The quantitative method provided in this project shows a possible way of visualizing and evaluating research community structure and thus a computerized calculation is possible for potential quantitative applications on open innovation research management, e.g. R&D resource allocation, research performance evaluation, and science map.


title: Changes in coagulation and fibrinolysis of post-SARS osteonecrosis in a Chinese population

text: The purpose of this study was to detect changes in coagulation and fibrinolysis of post-severe acute respiratory syndrome (SARS) Chinese patients with osteonecrosis, investigate the aetiology of post-SARS osteonecrosis (ON), and select the sensitive molecular markers for identifying the susceptible population. For this study, blood samples were collected from 88 patients with post-SARS ON and 52 healthy people. Activated partial thromboplastin time (APTT), protein C (PC), antithrombin III (AT–III), plasminogen activator inhibitor (PAI), activated protein C resistance (APC–R), plasminogen (PLG), von Willebrand’s factor(vWF), D–dimer (D–D), fibrinogen (Fib), and homocysteine (HCY) were examined by enzyme-linked immunosorbent assay (ELISA). We noted that blood agents of patients with ON changed obviously. APTT, PC, AT–III, PAI, APC–R, and PLG were significantly different between the two groups. Hypercoagulation and hypofibrinolysis were found in patients with post-SARS ON. Therefore, these examinations can be used to screen a population susceptible to ON. Measurements of APTT, PC, AT–III, PAI, APC–R, and PLG are sensitive blood tests for screening purposes.


title: Respiratory viral infections in institutions from late stage of the first and second waves of pandemic influenza A (H1N1) 2009, Ontario, Canada

text: Please cite this paper as: Asner et al. (2012) Respiratory viral infections in institutions from late stage of the first and second waves of pandemic A (H1N1) 2009, Ontario, Canada. Influenza and Other Respiratory Viruses 6(3), e11–e15. We report the impact of respiratory viruses on various outbreak settings by using surveillance data from the late first and second wave periods of the 2009 pandemic. A total of 278/345(78·5%) outbreaks tested positive for at least one respiratory virus by multiplex PCR. We detected A(H1N1)pdm09 in 20·6% of all reported outbreaks of which 54·9% were reported by camps, schools, and day cares (CSDs) and 29·6% by long‐term care facilities (LCFTs), whereas enterovirus/human rhinovirus (ENT/HRV) accounted for 62% outbreaks of which 83·7% were reported by long‐term care facilities (LCTFs). ENT/HRV was frequently identified in LTCF outbreaks involving elderly residents, whereas in CSDs, A(H1N1)pdm09 was primarily detected.


A classification of the aims of vaccination and its relevance to transgenerational justice


title: Respiratory Viral Pathogens

text: Respiratory viruses are responsible for a variety of clinical syndromes including the common cold, acute otitis media, laryngitis, sinusitis, pneumonia, bronchiolitis, influenza-like illness, and exacerbations of asthma and chronic obstructive pulmonary disease. Diagnosis of respiratory viral infections is primarily clinical and is further supported by laboratory techniques such as antigen detection, serology, and nucleic acid detection. Preventive strategies are based on avoidance of risk factors and, in case of influenza, vaccination. Treatment modalities include over-the-counter and non-specific remedies along with a small number of specific antiviral medications such as the influenza neuraminidase inhibitors or palivizumab against respiratory syncytial virus.


G6PD deficiency in COVID-19 pandemic: “a ghost in the ghost”


title: Human Cytomegalovirus Entry into Dendritic Cells Occurs via a Macropinocytosis-Like Pathway in a pH-Independent and Cholesterol-Dependent Manner

text: Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to infect fibroblastic, epithelial, endothelial and hematopoietic cells. Over the past ten years, several groups have provided direct evidence that dendritic cells (DCs) fully support the HCMV lytic cycle. We previously demonstrated that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) has a prominent role in the docking of HCMV on monocyte-derived DCs (MDDCs). The DC-SIGN/HCMV interaction was demonstrated to be a crucial and early event that substantially enhanced infection in trans, i.e., from one CMV-bearing cell to another non-infected cell (or trans-infection), and rendered susceptible cells fully permissive to HCMV infection. Nevertheless, nothing is yet known about how HCMV enters MDDCs. In this study, we demonstrated that VHL/E HCMV virions (an endothelio/dendrotropic strain) are first internalized into MDDCs by a macropinocytosis-like process in an actin- and cholesterol-dependent, but pH-independent, manner. We observed the accumulation of virions in large uncoated vesicles with endosomal features, and the virions remained as intact particles that retained infectious potential for several hours. This trans-infection property was specific to MDDCs because monocyte-derived macrophages or monocytes from the same donor were unable to allow the accumulation of and the subsequent transmission of the virus. Together, these data allowed us to delineate the early mechanisms of the internalization and entry of an endothelio/dendrotropic HCMV strain into human MDDCs and to propose that DCs can serve as a "Trojan horse" to convey CMV from entry sites to other locations that may favor the occurrence of either latency or acute infection.


title: Development and comparison of enzyme-linked immunosorbent assays based on recombinant trimeric full-length and truncated spike proteins for detecting antibodies against porcine epidemic diarrhea virus

text: BACKGROUND: Since 2010, outbreaks of genotype 2 (G2) porcine epidemic diarrhea virus (PEDV) have caused high mortality in neonatal piglets and have had devastating impacts on the swine industry in many countries. A reliable serological assay for evaluating the PEDV-specific humoral and mucosal immune response is important for disease survey, monitoring the efficacy of immunization, and designing strategies for the prevention and control of PED. Two PEDV spike (S) glycoprotein-based indirect enzyme-linked immunosorbent assays (ELISAs) were developed using G2b PEDV-Pintung 52 (PEDV-PT) trimeric full-length S and truncated S(1–501) proteins derived from the human embryonic kidney (HEK)-293 cell expression system. The truncated S(1–501) protein was selected from a superior expressed stable cell line. The sensitivity and specificity of these two ELISAs were compared to immunostaining of G2b PEDV-PT infected cells and to a commercial nucleocapsid (N)-based indirect ELISA kit using a panel of PEDV negative and hyperimmune sera. RESULTS: The commercial N-based ELISA exhibited a sensitivity of 37%, a specificity of 100%, and a fair agreement (kappa = 0.37) with the immunostaining result. In comparison, the full-length S-based ELISA showed a sensitivity of 97.8%, a specificity of 94%, and an almost perfect agreement (kappa = 0.90) with the immunostaining result. Interestingly, the S(1–501)-based ELISA had even higher sensitivity of 98.9% and specificity of 99.1%, and an almost perfect agreement (kappa = 0.97) with the immunostaining result. A fair agreement (kappa< 0.4) was seen between the commercial N-based ELISA and either of our S-based ELISAs. However, the results of the full-length S-based ELISA shared an almost perfect agreement (kappa = 0.92) with that of S(1–501)-based ELISA. CONCLUSIONS: Both full-length S-based and S(1–501)-based ELISAs exhibit high sensitivity and high specificity for detecting antibodies against PEDVs. Considering the high protein yield and cost-effectiveness, the S(1–501)-based ELISA could be used as a reliable, sensitive, specific, and economic serological test for PEDV.


title: Bat Migration ☆

text: Abstract This article summarizes current knowledge about the migratory behavior of temperate and tropical bats. A close association between migration and hibernation exists in temperate, but not in tropical, bats. Compared with birds, bats are relatively short-distance migrators, with maximum migration distances being <2000 km; intercontinental migration is likely to be uncommon in bats. Migratory bats have lower levels of population subdivision and larger genetically effective population sizes than nonmigratory bats. A variety of methods, including banding, genetic analyses, stable isotope analyses, and tracking with radio or satellite transmitters, are currently being used to study bat migration. The conservation of migratory bats poses special challenges that require national and international efforts. Migratory bats sometimes harbor pathogens that can be transmitted to humans. Overall, the beneficial aspects of migratory bats, including control of insect populations and dispersal of pollen and seeds over broad areas, far outweigh their negative aspects.


COVID‐19 Dashboard Helps Associations Think Proactively


title: Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India

text: Abstract Early and rapid detection of dengue virus (DENV) infection during the acute phase of illness is crucial for proper patient management and prevention of the spread of the infection. In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. The performance of the RT-LAMP was compared to RT-PCR, CDC 1-4 Real time PCR and the NS1 antigen ELISA, IgM and IgG anti DENV antibodies. Acute DENV infection was confirmed in 250/300 patients suspected clinically of DENV infection. RT- LAMP and CDC 1-4 Real time PCR assay was positive in 148/250 patients, while 92/250 patients were positive for anti- Dengue IgM and IgG antibodies. The RT-LAMP assay and the CDC real-time RT-PCR assay showed high concordance (k =1.0). The detection rate of acute DENV infection improved to 96% (240/250) when the results of RT-LAMP were combined with NS1 Ag, IgM and IgG ELISA. The RT-LAMP had a detection limit of 100 copies for DEN-1 and DEN-2, 10 copies for DEN-3 and DEN-4 compared to 1000 copies for DEN-1 and DEN-2, 100 copies for DEN-3 and DEN-4 by the conventional RT-PCR. The assay showed 100% specificity. The RT-LAMP assay developed in this study has potential use for early clinical diagnosis, serotyping and surveillance of DENV infection in endemic countries such as India.


title: Understanding Covid-19 Transmission: The Effect of Temperature and Health Behavior on Transmission Rates

text: BACKGROUND: Covid-19 pandemic is an uncharted territory for the world’s population. Countries are seeing measures they would have never considered under democratic governance in an attempt to contain case numbers. The role of outside air temperatures have been implicated as a potential factor involved in disease transmission. However, to this date, there has been no clear evidence to suggest either way. Along with temperatures, infection control and protection measures as well as how well people adopt these measures are likely to play a role in disease transmission and case growth rates seen across countries. METHODS: The current study uses panel data estimation for the original EU-15 countries in an attempt to explain the role of outside air temperatures, health behavior and government-imposed containment measures on Covid-19 transmission rates. RESULTS: The preliminary evidence suggests that containment measures are highly effective in slowing down the spread of Covid-19. Years of education also appears to have a small but negative association with disease transmission rates suggesting that populations with higher educational attainments may be doing a better job of self-protection. Temperature appears to have a very small, but statistically significant impact on the viral transmission rate where a 1 degree Celsius increase in temperatures is estimated to reduce Covid-19 transmission by 0.9 percent. CONCLUSION: Results are robust and clear. Temperature plays a small but significant role on Covid-19 transmission rates. However, it is quite possible that we may not have yet reached temperatures which may exert more pronounced effects on viral activity. Further research is warranted when more data becomes available, especially covering the months of July and August.


title: Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

text: Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.


title: Is Sub-Saharan Africa prepared for COVID-19?

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is the latest virus to cause global health panic. Due to the rapidly escalating numbers of new infections outside China, COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020, in a message delivered by Dr. Tedros Adhanom Ghebreyesus, the WHO Director-General [1]. As of March 21, about 166 countries globally had recoded cases of the COVID-19 in only 4 months since its outbreak in Wuhan, Hubei Province, China [2, 3]. With the Antarctic continent unaffected, Africa, in particular Sub-Saharan Africa (SSA), has recorded the least number of cases, despite the cited moderate-to-high risk of infection [4]. The biggest challenge is whether Sub-Saharan Africa is ready for this pandemic.


title: Cell penetrating peptide conjugates of steric block oligonucleotides

text: Abstract Charge neutral steric block oligonucleotide analogues, such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligomers (PMO), have promising biological and pharmacological properties for antisense applications, such as for example in mRNA splicing redirection. However, cellular uptake of free oligomers is poor and the utility of conjugates of PNA or PMO to cell penetrating peptides (CPP), such as Tat or Penetratin, is limited by endosomal sequestration. Two new families of arginine-rich CPPs named (R-Ahx-R)4 AhxB and R6Pen allow efficient nuclear delivery of splice correcting PNA and PMO at micromolar concentrations in the absence of endosomolytic agents. The in vivo efficacy of (R-Ahx-R)4 AhxB PMO conjugates has been demonstrated in mouse models of Duchenne muscular dystrophy and in various viral infections.


title: One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation

text: Abstract Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cis–trans isomerase (PPIase) activity inhibition assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could inhibit mouse spleen cell proliferation induced by concanavalin A (Con A). Molecular docking simulation further elucidated the specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor based on CypA inhibitor.


title: SARS-CoV and Emergent Coronaviruses: Viral Determinants of Interspecies Transmission

text: Most new emerging viruses are derived from strains circulating in zoonotic reservoirs. Coronaviruses, which had an established potential for cross-species transmission within domesticated animals, suddenly became relevant with the unexpected emergence of the highly pathogenic human SARS-CoV strain from zoonotic reservoirs in 2002. SARS-CoV infected approximately 8000 people worldwide before public health measures halted the epidemic. Supported by robust time-ordered sequence variation, structural biology, well-characterized patient pools, and biological data, the emergence of SARS-CoV represents one of the best studied natural models of viral disease emergence from zoonotic sources. This review article summarizes previous and more recent advances into the molecular and structural characteristics, with particular emphasis on host-receptor interactions, that drove this remarkable virus disease outbreak in human populations.


title: Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS

text: Summary Background The outbreak of severe acute respiratory syndrome (SARS) in 2002 was caused by a previously unknown coronavirus—SARS coronavirus (SARS-CoV). We have developed an experimental SARS vaccine for direct immunisation of the respiratory tract, the major site of SARS-coronavirus transmission and disease. Methods We expressed the complete SARS coronavirus envelope spike (S) protein from a recombinant attenuated parainfluenza virus (BHPIV3) that is being developed as a live attenuated, intranasal paediatric vaccine against human parainfluenza virus type 3 (HPIV3). We immunised eight African green monkeys, four with a single dose of BHPIV3/SARS-S and four with a control, BHPIV3/Ctrl, administered via the respiratory tract. A SARS-coronavirus challenge was given to all monkeys 28 days after immunisation. Findings Immunisation of animals with BHPIV3/SARS-S induced the production of SARS-coronavirus-neutralising serum antibodies, indicating that a systemic immune response resulted from mucosal immunisation. After challenge with SARS coronavirus, all monkeys in the control group shed SARS coronavirus, with shedding lasting 5–8 days. No viral shedding occurred in the group immunised with BHPIV3/SARS-S. Interpretation A vectored mucosal vaccine expressing the SARS-coronavirus S protein alone may be highly effective in a single-dose format for the prevention of SARS.


title: Epidemiological Characteristics of Notifiable Infectious Diseases among Foreign Cases in China, 2004–2017

text: Abstract Objective We aimed to assess the features of notifiable infectious diseases found commonly in foreign nationals in China between 2004 and 2017 to improve public health policy and responses for infectious diseases. Methods We performed a descriptive study of notifiable infectious diseases among foreigners reported from 2004 to 2017 in China using data from the Chinese National Notifiable Infectious Disease Reporting System (NNIDRIS). Demographic, temporal-spatial distribution were described and analyzed. Results A total of 67,939 cases of 33 different infectious diseases were reported among foreigners. These diseases were seen in 31 provinces of China and originated from 146 countries of the world. The infectious diseases with the highest incidence number were human immunodeficiency virus (HIV) of 18,713 cases, hepatitis B (6,461 cases), hand, foot, and mouth disease (6,327 cases). Yunnan province had the highest number of notifiable infectious diseases in foreigners. There were different trends of the major infectious diseases among foreign cases seen in China and varied among provinces. Conclusions This is the first description of the epidemiological characteristic of notifiable infectious diseases among foreigners in China from 2004 to 2017. These data can be used to better inform policymakers about national health priorities for future research and control strategies.


title: A fast and simple one-step duplex PCR assay for canine distemper virus (CDV) and canine coronavirus (CCoV) detection

text: The one-step polymerase chain reaction (one-step PCR) detection assay is an innovative PCR detection method, eliminating nucleic acid extraction steps, in which samples can be directly added to PCR reagents for testing. For simultaneous detection of CDV and CCoV, a sensitive and specific one-step duplex PCR (one-step dPCR) assay was developed with two pairs of primers that were designed based on H and M gene sequences of CDV and CCoV, respectively. The one-step dPCR with optimized detection conditions has high specificity and sensitivity; independent sequencing assays further verified these results.


title: An unusual cluster of HIV-1 B/F recombinants in an Asian population

text: Summary We report the detection of multiple HIV strains in injection drug users (IDU) in Macao, which appear to be derived from subtypes F, G, and CRF12_BF. A total of 14 HIV-infected IDU samples were collected and examined. Direct sequencing was performed to obtain the gag, pol, and env fragments. The subtypes of individual viral sequences were determined using the REGA subtyping tool. The concatenated sequences were aligned with reference sequences retrieved from the Los Alamos National Laboratory HIV database. We found 11 unusual cases in Macao, which showed characteristics of CRF12_BF (n =2) and CRF14_BG (n =8), and one that could not be classified into an existing subtype/CRF, along with three cases of CRF01_AE. Interestingly, the sequences derived from subtypes BG and BF recombinants have not been previously reported in any other Asian cities. Another subtype, CRF14_BG, has also been introduced into Macao among the IDUs. In conclusion, human activity, including travel over long distances and injection drug usage have fueled the spread of HIV and have provided a platform for recombination, which may otherwise have taken years to happen.


title: Monitoring epidemic viral respiratory infections using one‐step real‐Time Triplex RT‐PCR targeting influenza A and B viruses and respiratory syncytial virus

text: Rapid and specific diagnosis of influenza A/B and respiratory syncytial virus (RSV) viruses is needed for optimal management of patients with acute respiratory infections. In this study, a one‐step triplex real‐time RT‐PCR assay was developed for rapid diagnosis of influenza A/B and RSV infections to optimize diagnosis efficiency of acute respiratory infections. Cell‐culture supernatants and clinical samples were used to evaluate specificity and sensitivity of the assay. The assay was used routinely during two winter epidemics for testing respiratory specimens from 2,417 patients. The limit of detection in cell‐culture supernatant was 1–10 plaque forming units/input (influenza A/B) and 2 × 10(−2) 50% tissue culture infectious dose/input (RSV). In clinical samples, the assay was as sensitive as commercial molecular assays for the detection of each influenza A/B and RSV (Flu‐A/B and RSV‐A/B r‐gene™) individually, and far more sensitive than antigen detection. During the winter 2008–2009, the assay identified 145 RSV, 42 influenza A, and one mixed RSV‐influenza A infections among 298 patients. The next winter, the assay was used in two independent hospital laboratory settings. 776 patients were tested in one hospital and 1,343 in the other, resulting in 184 and 501 RSV, 133 and 150 influenza A, and 1 and 11 mixed RSV‐influenza A infections, respectively, being detected. This new user‐friendly assay allows rapid (within hours), effective molecular diagnosis of single or mixed infections involving influenza A (including seasonal A H1N1 and H3N2, and A(H1N1) 2009), influenza B, and RSV(A/B). The assay is very valuable for managing patients during winter epidemics when influenza and respiratory syncytial viruses co‐circulate. J. Med. Virol. 83:695–701, 2011. © 2011 Wiley‐Liss, Inc.


title: Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail

text: Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola – one from genetically-humanized mice, and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the SARS-CoV-2 spike protein, yielding a large collection of fully-human antibodies that were characterized for binding, neutralization and three dimensional structure. Based on these criteria, we selected pairs of highly-potent individual antibodies that simultaneously bind the receptor-binding domain of the spike protein, providing ideal partners for a therapeutic antibody cocktail that aims to decrease the potential for virus escape mutants that might arise in response to selective pressure from a single antibody treatment.


title: Histo-blood group glycans in the context of personalized medicine

text: Abstract Background A subset of histo-blood group antigens including ABO and Lewis are oligosaccharide structures which may be conjugated to lipids or proteins. They are known to be important recognition motifs not only in the context of blood transfusions, but also in infection and cancer development. Scope of review Current knowledge on the molecular background and the implication of histo-blood group glycans in the prevention and therapy of infectious and non-communicable diseases, such as cancer and cardiovascular disease, is presented. Major conclusions Glycan-based histo-blood groups are associated with intestinal microbiota composition, the risk of various diseases as well as therapeutic success of, e.g., vaccination. Their potential as prebiotic or anti-microbial agents, as disease biomarkers and vaccine targets should be further investigated in future studies. For this, recent and future technological advancements will be of particular importance, especially with regard to the unambiguous structural characterization of the glycan portion in combination with information on the protein and lipid carriers of histo-blood group-active glycans in large cohorts. General significance Histo-blood group glycans have a unique linking position in the complex network of genes, oncodevelopmental biological processes, and disease mechanisms. Thus, they are highly promising targets for novel approaches in the field of personalized medicine. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.


title: Does public ownership of utilities matter for local government water policies?

text: Abstract What differentiates local governments that implement water policies on equity and the environment? Analyzing a 2015 national survey of 1,897 U.S. municipalities, we find municipalities that own their water utilities are more likely to report policies to protect low-income residents from disconnection and implement water resource management. Respondents from 8% of municipalities report protecting residents from disconnection. State economic regulation of publicly owned utilities and Democrat-majority municipal governments are positively associated with local policies to protect low-income households from shutoffs but bear no association with resource management. Both local public ownership of utilities and state economic regulation may play a role in meeting certain local water policy goals.


title: Processing of the Coronavirus MHV-JHM Polymerase Polyprotein: Identification of Precursors and Proteolytic Products Spanning 400 Kilodaltons of ORF1a

text: Abstract The replicase of mouse hepatitis virus strain JHM (MHV-JHM) is encoded by two overlapping open reading frames, ORF1a and ORF1b, which are translated to produce a 750-kDa precursor polyprotein. The polyprotein is proposed to be processed by viral proteinases to generate the functional replicase complex. To date, only the MHV-JHM amino-terminal proteins p28 and p72, which is processed to p65, have been identified. To further elucidate the biogenesis of the MHV-JHM replicase, we cloned and expressed five regions of ORF1a in bacteria and prepared rabbit antisera to each region. Using the immune sera to immunoprecipitate radiolabeled proteins from MHV-JHM infected cells, we determined that the MHV-JHM ORF1a is initially processed to generate p28, p72, p250, and p150. Pulse–chase analysis revealed that these intermediates are further processed to generate p65, p210, p40, p27, the MHV 3C-like proteinase, and p15. A putative replicase complex consisting of p250, p210, p40, p150, and a large protein (>300 kDa) coprecipitate from infected cells disrupted with NP-40, indicating that these proteins are closely associated even after initial proteolytic processing. Immunofluorescence studies revealed punctate labeling of ORF1a proteins in the perinuclear region of infected cells, consistent with a membrane-association of the replicase complex. Furthermore,in vitrotranscription/translation studies of the MHV-JHM 3Cpro and flanking hydrophobic domains confirm that 3C protease activity is significantly enhanced in the presence of canine microsomal membranes. Overall, our results demonstrate that the MHV-JHM ORF1a polyprotein: (1) is processed into more than 10 protein intermediates and products, (2) requires membranes for efficient biogenesis, and (3) is detected in discrete membranous regions in the cytoplasm of infected cells.


title: Swine intestine antimicrobial peptides inhibit infectious bronchitis virus infectivity in chick embryos

text: Infectious bronchitis virus (IBV), the causative agent of infectious bronchitis, results in respiratory disease, nephritis, and poor egg production and quality in chicken. Antimicrobial peptides possess potent antimicrobial activities and are regarded as promising therapeutic alternatives in the fight against microorganisms. To assess the in vitro antiviral activity of swine intestine antimicrobial peptides (SIAMP) against IBV, 45 chick embryos were randomly assigned into 3 groups, 15 for each group. Embryos in group 1 were inoculated with IBV. Group 2 was inoculated with SIAMP-IBV intermixture. Group 3 was used as a control and inoculated with sterile PBS. Allantoic fluid was collected for hemagglutination titer assay. In addition, weight gain, mortality, and pathological changes for each group were recorded. The results showed that no distinct pathological changes were found in chick embryos after they were inoculated with SIAMP-IBV intermixture and the mortality was reduced remarkably compared with the IBV-infected group. Weight gain of embryos in the SIAMP-IBV intermixture group was significantly higher than the IBV-infected embryos (P < 0.01), which was also higher than the control group (P < 0.05). Furthermore, the hemagglutination titer in the SIAMP-IBV group was significantly lower than that in the IBV-infected group (P < 0.01). These results indicated that SIAMP can inhibit virus replication and reduce tissue injury caused by IBV.


title: Respiratory Diseases of Rodents

text: Practitioners may be called on to treat rodents with respiratory diseases or to advise clients concerning the care of these rodents. Respiratory diseases of mice, rats, guinea pigs, and Syrian hamsters are well known because of the use of these species in research, whereas few or no reports of respiratory disease in rodents of other species exist. Features of the respiratory diseases of these four commonly encountered species are reviewed, including causes; clinical signs; diagnostic procedures; preventive measures; and, where appropriate, therapies.


COVID-19 Outbreak: the gold rush and the Responsibilities of the scientific community


Returning to elective surgery, the ‘new normal’


title: Sequence comparison via polar coordinates representation and curve tree

text: Abstract Sequence comparison has become one of the essential bioinformatics tools in bioinformatics research, which could serve as evidence of structural and functional conservation, as well as of evolutionary relations among the sequences. Existing graphical representation methods have achieved promising results in sequence comparison, but there are some design challenges with the graphical representations and feature-based measures. We reported here a new method for sequence comparison. It considers whole distribution of dual bases and employs polar coordinates method to map a biological sequence into a closed curve. The curve tree was then constructed to numerically characterize the closed curve of biological sequences, and further compared biological sequences by evaluating the distance of the curve tree of the query sequence matching against a corresponding curve tree of the template sequence. The proposed method was tested by phylogenetic analysis, and its performance was further compared with alignment-based methods. The results demonstrate that using polar coordinates representation and curve tree to compare sequences is more efficient.


title: China-Africa Health Development Initiatives: Benefits and Implications for Shaping Innovative and Evidence-informed National Health Policies and Programs in Sub-saharan African Countries

text: BACKGROUND AND INTRODUCTION: This review paper examines the growing implications of China’s engagement in shaping innovative national initiatives against infectious diseases and poverty control and elimination in African countries. It seeks to understand the factors and enhancers that can promote mutual and innovative health development initiatives, and those that are necessary in generating reliable and quality data for evidence-based contextual policy, priorities and programs. METHODS: We examined the China-Africa health cooperation in supporting global health agenda on infectious diseases such as malaria, schistosomiasis, Ebola, TB, HIV/AIDS, neglected tropical diseases (NTDs) prevention, control and elimination spanning a period of 10 years. We reviewed referenced publications, global support data, and extensive sources related to and other emerging epidemics and infectious diseases of poverty, programs and interventions, health systems development issues, challenges, opportunities and investments. Published literature in PubMed, Scopus, Google Scholar, Books and web-based peer-reviewed journal articles, government annual reports were assessed from the first Forum on China-Africa Cooperation (FOCAC) in November 2006 to December 2015 Third Ministerial conferences. RESULTS: Our findings highlight current shared public health challenges and emphasize the need to nurture, develop and establish effective, functional and sustainable health systems capacity to detect and respond to all public health threats and epidemic burdens, evidence-based programs and quality care outcomes. China’s significant health diplomacy emphasizes the importance of health financing in establishing health development commitment and investment in improving the gains and opportunities, importantly efficiency and value health priorities and planning. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Strengthening China-Africa health development agenda towards collective commitment and investment in quality care delivery, effective programs coverage and efficiency, preparedness and emergency response is needed in transforming African health information systems, and local health governance structures and management in emerging epidemics. Furthermore, innovative evidence of operational joint solutions and strategies are critical in advancing healthcare delivery, and further enhancing Universal Health Care, and Sustainable Development Goals to attain global health improvements and economic prosperity.


title: Can graphene take part in the fight against COVID-19?

text: Abstract The pneumonia outbreak of coronavirus disease 2019 (COVID-19) represents a global issue. The bidimensional material graphene has captured much attention due to promising antimicrobial applications and has also demonstrated antiviral efficacy. In response to this global outbreak, we summarized the current state of knowledge of graphene and virus interaction as well as possible successful applications to fight COVID-19. Antibody-conjugated graphene sheets can rapidly detect targeted virus proteins and can be useful for large population screening, but also for the development of environmental sensors and filters, given the low cost of graphene materials. The functionalized graphene has demonstrated a good viral capture capacity that, combined with heat or light-mediated inactivation, could be used as a disinfectant. Graphene sensors arrays can be implemented on standard utility textiles and drug efficacy screening. Thanks to its high versatility, we foresee that graphene may have a leading role in the fight against COVID-19.


title: Data on social and health vulnerability in rural India: A Case of Covid-19

text: An attempt was made to understand the gap between health and social vulnerability to Covid-19 pandemic. By using multistage sampling technique, 150 samples were collected during February and March 2020. Data highlight that households are highly exposed to novel Covid-19 and also equally sensitive to inadequate and poor availability and accessibility of clean water, sanitation and health care system. Data suggest a grass root awareness programme (ex-ante preventive measures) in the regional languages; increase public health budget to meet the demand and improve the supply chain; establishment of more physical and human infrastructure in long run; comprehensive plan to ensure continuous water supply in the rural areas.


title: Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis

text: OBJECTIVE: Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. METHODS: Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. RESULTS: There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I(2) 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I(2) 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I(2) 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I(2) 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I(2) 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I(2) 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). CONCLUSION: This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.


Predicted value of coagulation function for prognosis and admission time to negative RT‐PCR detection in non‐critical COVID‐19 patients