title: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China

text: AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers’ case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.


title: Pathogenic murine coronaviruses II. Characterization of virus-specific proteins of murine coronaviruses JHMV and A59V

text: Abstract We have identified nine intracellular virus-specific proteins in cells infected with JHMV or A59V. Seven virus-specific proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two additional virus-specific proteins were detected by two-dimensional gel electrophoresis. The A59V- and JHMV-specific proteins differ slightly in molecular weight. Four of the nine proteins are structural proteins. The synthesis of the nine virus-specific proteins is noncoordinate with respect to time.


title: Cathepsin L Helps to Defend Mice from Infection with Influenza A

text: Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl(-/-) mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl(+/+) mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl(-/-) and Ctsl(+/+) mice, although Ctsl(+/+) mice cleared immunoreactive virus sooner. Furthermore, Ctsl(-/-) mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.


title: Management of newborns exposed to mothers with confirmed or suspected COVID-19

text: There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother–newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.


title: CORONAVIRUS – COVID 19: Más allá de la enfermedad pulmonar, qué es y qué sabemos del vínculo con el sistema cardiovascular

text: Resumen La infección por SARS-CoV2 es una pandemia. Se creía que el primer caso de esta enfermedad ocurrió el 8 de diciembre de 2019 en la provincia de Hubei en China, aunque posteriormente se indicó que el primer caso confirmado por laboratorio ocurrió el 1.º de diciembre de 2019 ante la presencia de un brote de neumonía en 59 pacientes sospechosos en un mercado local de mariscos en Wuhan. No solo produce patología respiratoria, con frecuencia compremete el sistema cardiovascular ya que produce lesión miocárdica, miocarditis, y, con cierta frecuencia, aumenta la descompensación de enfermedades cardiovasculares preestablecidas. En este artículo se trata de dilucidar el componente cardiovascular hasta ahora existente en la literatura y se sugieren algunos pasos a seguir en pacientes con estas enfermedades, acorde con la evidencia actual. Abstract Infection due to SARS-CoV2 is a pandemic. It is believed that the first case occurred on 8 December 2019 in Hubei province in China, although it was later indicated that the first laboratory-confirmed case occurred on 1 December 2019 due to the presence of an outbreak of suspected pneumonia in 59 patients in a shellfish market in Wuhan. It not only caused a respiratory disease, it often compromised the cardiovascular system since it produces a myocardial lesion, myocarditis, and, less often, increased the decompensation of pre-established cardiovascular diseases. An attempt is made in this article to elucidate the cardiovascular component presented in the current literature, and to suggest some steps to follow in patients with these diseases in accordance with the current evidence.


The Human Genome and Advances in Medicine: Limits and Future Prospects


title: Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship

text: OBJECTIVES: To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3(pro)) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship. RESULTS: ZIKV NS2B-NS3(pro) was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K (m) of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3(pro) was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3(pro) by 6.2–88%. Seven polyphenol compounds had IC(50) ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3(pro) protease. Its IC(50) value was 22 ± 0.2 µM with a K (i) value of 8.9 ± 1.9 µM. CONCLUSION: The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3(pro) can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-016-2261-6) contains supplementary material, which is available to authorized users.


title: A cluster of patients with severe acute respiratory syndrome in a chest ward in southern Taiwan

text: OBJECTIVE: Severe acute respiratory syndrome (SARS) is an emerging and easily clustering infectious disease. We describe an outbreak of SARS in a chest ward of a medical center in southern Taiwan and seek to identify the risk factors of those SARS patients who required mechanical ventilation. We focus on previous health patients. DESIGN: This retrospective case series was collected during the SARS outbreak. Degrees of severity were established, based on whether intubation and mechanical ventilation was necessary. SETTING: A 2500-bed medical center in southern Taiwan. PATIENTS: Forty-four patients exhibited symptoms that met the modified World Health Organization (WHO) definition of SARS. These included of three subgroups: health-care workers (n=16), relatives (n=14), and patients already admitted for other ailments (n=14). Of these, 20 eventually required mechanical ventilation. MEASUREMENTS AND RESULTS: Laboratory analyses showed statistically significant differences between intubated and nonintubated patients in white blood cell count, neutrophil percentage, and C-reactive protein level as well as in age and underlying malignancy. Risk factors for SARS patients who had been healthy prior to their illness included old age, high peak fever grade, increased neutrophil count, increased neutrophil percentage, and close or prolonged contact with a SARS patient. CONCLUSIONS: Old age, high white blood cell counts, high peak grade fever, and close or prolonged contact with a SARS patient increase the risk of intubation in previous healthy SARS patients.


title: Why Isn’t Latvia the “Next” Crimea? Reconsidering Ethnic Integration

text: Abstract In the aftermath of Russia's military incursion in Ukraine and the annexation of Crimea in 2014, a flurry of articles predicted the next territorial conquest of President Vladimir Putin's Russian revanchism. High on the list were the Baltic countries, which sit precariously on the edge of Europe and historically have been the “bloodlands” between East and West in author Timothy Snyder's phrasing. More specifically, journalists and analysts pointed to the “Russian enclaves” in northeastern Estonia and southeastern Latvia, where, by many accounts, large ethnic Russian populations were prepared to rise up against Baltic governments with a bit of provocation from across the eastern border. However, six years on, there is little indication that Russian speakers in the Baltic countries are on the brink of causing an internal uprising. While there are multiple factors that can help explain the Baltic “dog that didn’t bark,” this essay considers an often overlooked variable in the equation: the depth of civic and cultural integration among Russian speakers in Latvia.


title: Investigation of effective climatology parameters on COVID-19 outbreak in Iran

text: Abstract SARS CoV-2 (COVID-19) Coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. A better understanding of the effective parameters in infection spreading can bring about a logical measurement toward COVID-19. The effect of climatic factors on spreading of COVID-19 can play an important role in the new Coronavirus outbreak. In this study, the main parameters, including the number of infected people with COVID-19, population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on COVID-19 spreading in Iran? The Partial correlation coefficient (PCC) and Sobol’-Jansen methods are used for analyzing the effect and correlation of variables with the COVID-19 spreading rate. The result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. Conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. The provinces such as Tehran, Mazandaran, Alborz, Gilan, and Qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with Southern provinces.


Comments to the predecessor of human SARS coronavirus in 2003–2004 epidemic


title: Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury

text: Abstract Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as “cytokine storm”, occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.


title: Navigating the jungles of tropical infectious gastrointestinal pathology: a pattern-based approach to the endoscopic biopsy

text: International travels and global human migration have had the unforeseen consequence of increasing the exposure of histopathologists in developed countries to the pathology of tropical infectious disease. The gastrointestinal tract (GIT) is often the primary site of infection due to the faecal-oral route of transmission and the high risk of exposure to contaminated water, food or soil when travelling to these regions. Whilst current microbiologic techniques are far more sensitive than histology in detecting infectious pathogens, the histopathologist nonetheless retains a pivotal role in diagnosing tropical GIT disease. This role entails evaluating endoscopic biopsies for any characteristic inflammatory pattern, identifying pathogens which may be present and excluding other look-alike pathologies. Recent advances in commercially available diagnostic modalities, including molecular techniques, have further broadened the scope of the histopathologist’s armamentarium. This review outlines a practical pattern-based approach to diagnosing tropical GIT infections in endoscopic material, so as to assist pathologists less familiar with this spectrum of pathology.


title: New emergence pattern with variant porcine epidemic diarrhea viruses, South Korea, 2012–2015

text: Abstract Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014–2015year. This study analyzed a large collection of the Spike protein coding gene to infer the spatial-temporal diffusion history of PEDV. The studying results suggested that PEDVs in Korea belonged to different genogroups. While classical G1 was continuingly circulating between provinces of Korea, the pandemic G2a were recently introduced from China and USA. By the application of Bayesian phylogeographical analysis, this study demonstrated the spatial-temporal transmission of PEDVs within Korea. Of the recent emerged G2a viruses, J3142 strains showed potential recombination breakpoint (376–2,143nt) of S1 gene between KNU1303_Korea strain_G2a (KJ451046) and 45RWVCF0712_Thailand strain_G2b (KF724935). The pandemic G2a virus was partial neutralized by the antibodies invoked by the G1- based PED vaccine virus.


So geht Wiederbelebung in Corona-Zeiten


title: The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients

text: Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure.


title: Rapid generation of neutralizing antibody responses in COVID-19 patients

text: Summary SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating global pandemic and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.


title: Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen

text: BACKGROUND: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. RESULTS: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. CONCLUSION: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.


title: Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition)

text: In the early February, 2020, we called up an experts’ committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.


title: Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus

text: Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several ‘‘enabling pairs’’ of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC(50) >1 mM) to exhibit potent neutralization (IC(50) 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neu-tralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines.


The UK Public Health Association and Congress of the World Federation of Public Health Associations (WFPHA) conference—plenary session presentations


title: Seroprevalence of antibody to pandemic influenza A (H1N1) 2009 among healthcare workers after the first wave in Hong Kong

text: Summary During the first wave of an influenza pandemic prior to the availability of an effective vaccine, healthcare workers (HCWs) may be at particular risk of infection with the novel influenza strain. We conducted a cross-sectional study of the prevalence of antibody to pandemic influenza A (H1N1) 2009 (pH1N1) among HCWs in Hong Kong in February–March 2010 following the first pandemic wave. Sera collected from HCWs were tested for antibody to pH1N1 influenza virus by viral neutralisation (VN). We assessed factors associated with higher antibody titres, and we compared antibody titres in HCWs with those in a separate community study. In total we enrolled 703 HCWs. Among 599 HCWs who did not report receipt of pH1N1 vaccine, 12% had antibody titre ≥1:40 by VN. There were no significant differences in the age-specific proportions of unvaccinated HCWs with antibody titre ≥1:40 compared with the general community following the first wave of pH1N1. Under good adherence to infection control guidelines, potential occupational exposures in the hospital setting did not appear to be associated with any substantial excess risk of pH1N1 infection in HCWs. Most HCWs had low antibody titres following the first pandemic wave.


title: Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic

text: BACKGROUND: Confirmed H1N1 cases during late spring and summer 2009 in various countries showed a substantial age shift between importations and local transmission cases, with adults mainly responsible for seeding unaffected regions and children most frequently driving community outbreaks. METHODS: We introduce a multi-host stochastic metapopulation model with two age classes to analytically investigate the role of a heterogeneously mixing population and its associated non-homogeneous travel behaviors on the risk of a major epidemic. We inform the model with demographic data, contact data and travel statistics of Europe and Mexico, and calibrate it to the 2009 H1N1 pandemic early outbreak. We allow for variations of the model parameters to explore the conditions of invasion under different scenarios. RESULTS: We derive the expression for the potential of global invasion of the epidemic that depends on the transmissibility of the pathogen, the transportation network and mobility features, the demographic profile and the mixing pattern. Higher assortativity in the contact pattern greatly increases the probability of spatial containment of the epidemic, this effect being contrasted by an increase in the social activity of adults vs. children. Heterogeneous features of the mobility network characterizing its topology and traffic flows strongly favor the invasion of the pathogen at the spatial level, as also a larger fraction of children traveling. Variations in the demographic profile and mixing habits across countries lead to heterogeneous outbreak situations. Model results are compatible with the H1N1 spatial transmission dynamics observed. CONCLUSIONS: This work illustrates the importance of considering age-dependent mixing profiles and mobility features coupled together to study the conditions for the spatial invasion of an emerging influenza pandemic. Its results allow the immediate assessment of the risk of a major epidemic for a specific scenario upon availability of data, and the evaluation of the potential effectiveness of public health interventions targeting specific age groups, their interactions and mobility behaviors. The approach provides a general modeling framework that can be used for other types of partitions of the host population and applied to different settings.


title: Deciphering MERS-CoV Evolution in Dromedary Camels

text: The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) poses a potential threat to global public health. Many aspects of the evolution and transmission of MERS-CoV in its animal reservoir remain unclear. A recent study provides new insights into the evolution and transmission of MERS-CoV in dromedary camels.


title: Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

text: Summary SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal antibody in ferrets, which can be readily infected with the virus. Prophylactic administration of the monoclonal antibody at 10 mg/kg reduced replication of SARS coronavirus in the lungs of infected ferrets by 3·3 logs (95% Cl 2·6–4·0 logs; p<0·001), completely prevented the development of SARS coronavirus-induced macroscopic lung pathology (p=0·013), and abolished shedding of virus in pharyngeal secretions. The data generated in this animal model show that administration of a human monoclonal antibody might offer a feasible and effective prophylaxis for the control of human SARS coronavirus infection.


title: Molecular diagnosis of respiratory viruses

text: Summary The increasing availability of nucleic acid amplification tests since the 1980s has revolutionised our understanding of the pathogenesis, epidemiology, clinical and laboratory aspects of known and novel viral respiratory pathogens. High-throughput, multiplex polymerase chain reaction is the most commonly used qualitative detection method, but utilisation of newer techniques such as next-generation sequencing will become more common following significant cost reductions. Rapid and readily accessible isothermal amplification platforms have also allowed molecular diagnostics to be used in a ‘point-of-care’ format. This review focuses on the current applications and limitations of molecular diagnosis for respiratory viruses.


title: Chapter 9 Keeping Track of Viruses

text: Publisher Summary This chapter reviews methods of isolating, identifying, and tracking viruses with potential applications to microbial forensic investigations. Viruses are the most abundant biological entities on earth. These obligate parasites infect every form of life, from archaea and eubacteria to fungi, plants, and animals. Viruses play key roles in global ecology—they form a vast reservoir of genetic diversity, influence the composition and evolution of host populations, and affect the cycling of chemical compounds through the environment. Research has focused on the tiny fraction that causes disease in humans, domestic animals, and crops; sequencing surveys have suggested that the majority of viruses are completely unknown. The ability of viruses to jump species barriers, move between habitats, and circle the globe rapidly underscores the importance of continued vigilance for naturally emerging or deliberately engineered outbreaks. Viruses are extremely simple “life” forms without metabolic capacity, organelles, translational machinery, or autonomous replicative potential. Virus particles constitute a minimal set of components, primarily those required to deliver the genome to the target cell and initiate replication. Consequently, virus particles (or virions) are extremely small, most in the range of 20 to 200 nm in diameter. Virions are diverse not only in size but also in composition, morphology, and genome characteristics. Virus particles may be irregular in shape or possess a distinct symmetry, such as helical or icosahedral. Particles may be surrounded by a host-derived membrane, termed “enveloped,” or a tight protein shell, termed “nonenveloped.”


title: Surveillance of influenza in Apulia, Italy, 1999–2000, 2000–2001, 2001–2002, and 2002–2003 seasons

text: Abstract Background. – The objective of this study was to evaluate, within the Italian National Influenza Epidemiological and Virological Surveillance, the rate of vaccination coverage, the incidence of Influenza Like-Illness (ILI), the incidence of Acute Respiratory Illness (ARI), and to identify the virus strains circulating in Apulia from 1999 to 2003. Methods. – Vaccination coverage rates were calculated based on the number of doses administered to individuals >65 years of age. Every week, sentinel physicians reported ILI and ARI cases having occurred among their patients. Voluntary general practitioners (GPs) and paediatricians (Ps) collected oropharyngeal swab samples from patients suspected with ILI. Influenza viruses were isolated and identified by cell culture (MDCK cells) and RT-PCR. Virological surveillance was carried out by the ISS, in collaboration with a network of peripheral laboratories. Results. – In Apulia, vaccination coverage progressively increased to 68.6% during the 2002–2003 season. The analysis of ILI cases showed higher incidence rates during the 1999–2000 and 2002–2003 seasons. ARI rates appeared to have a more constant trend. ILI and ARI incidence rates were higher in the 0–14 year age group. Conclusion. – The increase in vaccination coverage rates and implementation of the network of clinical, and epidemiological and virological surveillance are fundamental for the control and prevention of influenza.


The Biodefense Field


title: Molecular and biological characteristics of the infectious bronchitis virus TC07-2/GVI-1 lineage isolated in China

text: Abstract In the present study, a thorough comparison of the infectious bronchitis virus (IBV) TC07–2/GVI-1 linage was conducted by comparing the S1 gene sequences of GVI-1 viruses with those of viruses representing the established genotypes and lineages. IBV GVI-1 strains were found to be closely genetically related to each other, irrespective of where the viruses were isolated, and differed from other known IBV genotypes and lineages; thus, it was confirmed that GVI represents a novel genotype. However, the GVI-1 viruses exhibited variable antigenicity when compared to each other. Further analysis found that strains CO8089L and CO8091L, which were isolated in Colombia in 2003, were closely related to GVI-1 viruses, suggesting that GVI-1 viruses likely originated from Colombia and are prevalent in at least five countries (Colombia, China, the Republic of Korea, Japan, and Vietnam). Analysis of the complete GVI-1 virus genomes suggested that the GVI-1 strains in China may be independently derived from recombination events that occurred between GI-19 strains and CO8089L/CO8091L-like viruses following the introduction of the viruses from Colombia. Similar to the viruses isolated in the Republic of Korea, GVI-1 viruses isolated in China also showed an affinity for the respiratory tract of chickens, which differed from one of the deduced parental viruses, the GI-19 strain. This difference may be due to recombination events that occurred in the genomes of the GVI-1 viruses, resulting in the replacement of the spike gene sequences in an YX10-like strain of GI-19 lineage.


title: Development of an inactivated candidate vaccine against Chandipura virus (Rhabdoviridae: Vesiculovirus)

text: A Vero cell based vaccine candidate against Chandipura (CHP) virus (Rhabdoviridae: Vesiculovirus), was developed and evaluated for immunogenicity in mice. Virus was purified by ultracentrifugation on 30% glycerol cushion followed by differential centrifugation on 10–60% sucrose gradient and inactivated with β-propio lactone at a concentration of 1:3500. The inactivated product was blended with aluminium phosphate (3%) and immunized 4-week-old Swiss albino mice. Neutralizing antibodies in the range of 1:10 to 160 and 1:80 to 1:320 was detected with 85% and 100% sero-conversion after 2nd and 3rd dose, respectively. All the immunized mice with antibody titer above 1:20 survived live virus challenge. The vaccine candidate has potential to be an efficient vaccine against CHP virus.


title: Viral journeys on the intracellular highways

text: Viruses are obligate intracellular pathogens that are dependent on cellular machineries for their replication. Recent technological breakthroughs have facilitated reliable identification of host factors required for viral infections and better characterization of the virus–host interplay. While these studies have revealed cellular machineries that are uniquely required by individual viruses, accumulating data also indicate the presence of broadly required mechanisms. Among these overlapping cellular functions are components of intracellular membrane trafficking pathways. Here, we review recent discoveries focused on how viruses exploit intracellular membrane trafficking pathways to promote various stages of their life cycle, with an emphasis on cellular factors that are usurped by a broad range of viruses. We describe broadly required components of the endocytic and secretory pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Identification of such overlapping host functions offers new opportunities to develop broad-spectrum host-targeted antiviral strategies.


title: Prioritizing Zoonoses for Global Health Capacity Building—Themes from One Health Zoonotic Disease Workshops in 7 Countries, 2014–2016

text: Zoonotic diseases represent critical threats to global health security. Effective mitigation of the impact of endemic and emerging zoonotic diseases of public health importance requires multisectoral collaboration and interdisciplinary partnerships. The US Centers for Disease Control and Prevention created the One Health Zoonotic Disease Prioritization Tool to help countries identify zoonotic diseases of greatest national concern using input from representatives of human health, agriculture, environment, and wildlife sectors. We review 7 One Health Zoonotic Disease Prioritization Tool workshops conducted during 2014–2016, highlighting workshop outcomes, lessons learned, and shared themes from countries implementing this process. We also describe the tool’s ability to help countries focus One Health capacity-building efforts to appropriately prevent, detect, and respond to zoonotic disease threats.


title: Chapter 5 Category C Diseases and Agents

text: Abstract This chapter covers Category C diseases and agents. These emerging diseases present a very unique challenge to public health officials and infectious disease specialists. Perhaps they have been with us for millions of years, lurking in a dark corner of the environment, waiting for an opportunity to jump from their natural cycle of transmission to a human host. Or they may represent something totally new. Regardless of their origin, an emerging disease pathogen must be characterized quickly by molecular biologists and microbiologists. The dynamics of disease transmission must be investigated by teams of epidemiologists. Treatment regimens must be formulated by clinicians working on the frontlines of the outbreak. Disease prevention strategies and risk communications must be quickly formulated by public health officials. Finally, media attention for emerging disease outbreaks forces government officials at all levels to address the problem with planning and preparedness activities aimed at preserving the health of the public. Specific examples explored in this chapter include Nipah virus, hantavirus, West Nile fever virus, and the coronaviruses that cause severe acute respiratory syndrome and Middle East respiratory syndrome.


title: Detection and Genetic Characterization of Deltacoronavirus in Pigs, Ohio, USA, 2014

text: In Ohio, United States, in early 2014, a deltacoronavirus was detected in feces and intestine samples from pigs with diarrheal disease. The complete genome sequence and phylogenetic analysis of the virus confirmed that the virus is closely related to a porcine deltacoronavirus (porcine coronavirus HKU15) reported in Hong Kong in 2012.


title: Brain angiotensin‐converting enzymes: role of angiotensin‐converting enzyme 2 in processing angiotensin II in mice

text: Angiotensin (Ang)‐converting enzyme 2 (ACE2) metabolizes Ang II to the vasodilatory peptide Ang(1–7), while neprilysin (NEP) generates Ang(1–7) from Ang I. Experiments used novel Surface Enhanced Laser Desorption Ionization‐Time of Flight (SELDI‐TOF) mass spectroscopic (MS) assays to study Ang processing. Mass spectroscopy was used to measure proteolytic conversion of Ang peptide substrates to their specific peptide products. We compared ACE/ACE2 activity in plasma, brain and kidney from C57BL/6 and NEP (−/−) mice. Plasma or tissue extracts were incubated with Ang I or Ang II (1296 or 1045, m/z, respectively), and generated peptides were monitored with MS. Angiotensin‐converting enzyme 2 activity was detected in kidney and brain, but not in plasma. Brain ACE2 activity was highest in hypothalamus. Angiotensin‐converting enzyme 2 activity was inhibited by the specific ACE2 inhibitor, DX600 (10 μm, 99% inhibition), but not by the ACE inhibitor, captopril (10 μm). Both MS and colorimetric assays showed high ACE activity in plasma and kidney with low levels in brain. To extend these findings, ACE measurements were made in ACE overexpressing mice. Angiotensin‐converting enzyme four‐copy mice showed higher ACE activity in kidney and plasma with low levels in hypothalamus. In hypothalamus from NEP (−/−) mice, generation of Ang(1–7) from Ang I was decreased, suggesting a role for NEP in Ang metabolism. With Ang II as substrate, there was no difference between NEP (−/−) and wild‐type control mice, indicating that other enzymes may contribute to generation of Ang(1–7). The data suggest a predominant role of hypothalamic ACE2 in the processing of Ang II, in contrast to ACE, which is most active in plasma.


title: Not just angiotensinases: new roles for the angiotensin-converting enzymes

text: The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Angiotensin II, the primary bioactive peptide of the RAS, is generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue of ACE, ACE2, is able to convert angiotensin II to a peptide with opposing effects, angiotensin-(1-7). It is proposed that disturbance of the balance of ACE and ACE2 expression and/or function is important in pathologies in which angiotensin II plays a role. These include cardiovascular and renal disease, lung injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating angiotensin II levels have traditionally focussed attention on their activities as angiotensinases. Recent discoveries, however, have illuminated the roles of these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking and signalling. This paper reviews the key literature regarding both the catalytic and non-catalytic roles of the angiotensin-converting enzyme gene family.


title: Evaluation of Alere i RSV for Rapid Detection of Respiratory Syncytial Virus in Children Hospitalized with Acute Respiratory Tract Infection

text: Alere i RSV is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. In this study, we evaluated the Alere i RSV assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. Alere i RSV assay results were compared to those for Altona RealStar RSV real-time reverse transcription-PCR (RT-PCR). We found that the overall sensitivity and specificity of the Alere i RSV test was 100% (95% confidence intervals [CI], 93% to 100%) and 97% (95% CI, 89% to 100%), respectively. Positive samples were identified within 5 to 7 min from sample collection. Overall, the Alere i RSV test performed well compared to the RT-PCR assay and has the potential to facilitate the detection of RSV in point-of-care settings.


title: Novel platinum(II) and palladium(II) complexes of thiosemicarbazones derived from 5-substitutedthiophene-2-carboxaldehydes and their antiviral and cytotoxic activities

text: A series of thiosemicarbazones and their platinum(II) and palladium(II) complexes have been synthesized. The chemical structures of ligands and their complexes were characterized by UV–Vis, IR, (1)H NMR, (13)C NMR, MS spectra, elemental analysis and TGA. The antiviral and cytotoxic activities of all compounds have been tested. Results of broad antiviral evaluation showed that none of the compounds evaluated endowed with anti-DNA or -RNA virus activity at subtoxic concentrations except for the palladium complex 1b. This compound exhibited slightly selective inhibition against cytomegalovirus. The platinum complex 4a exhibited the best cytostatic activities against human cervix carcinoma. Ligands 2, 4 and 5 showed cytostatic potential. The palladium complexes were in general less cytostatic than the corresponding platinum complexes or unliganded congeners.


title: Dry Taps? A Synthesis of Alternative “Wash” Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings

text: Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.


title: A novel enterovirus and parechovirus multiplex one-step real-time PCR-validation and clinical experience

text: Abstract As the number of new enteroviruses and human parechoviruses seems ever growing, the necessity for updated diagnostics is relevant. We have updated an enterovirus assay and combined it with a previously published assay for human parechovirus resulting in a multiplex one-step RT-PCR assay. The multiplex assay was validated by analysing the sensitivity and specificity of the assay compared to the respective monoplex assays, and a good concordance was found. Furthermore, the enterovirus assay was able to detect 42 reference strains from all 4 species, and an additional 9 genotypes during panel testing and routine usage. During 15 months of routine use, from October 2008 to December 2009, we received and analysed 2187 samples (stool samples, cerebrospinal fluids, blood samples, respiratory samples and autopsy samples) were tested, from 1546 patients and detected enteroviruses and parechoviruses in 171 (8%) and 66 (3%) of the samples, respectively. 180 of the positive samples could be genotyped by PCR and sequencing and the most common genotypes found were human parechovirus type 3, echovirus 9, enterovirus 71, Coxsackievirus A16, and echovirus 25. During 2009 in Denmark, both enterovirus and human parechovirus type 3 had a similar seasonal pattern with a peak during the summer and autumn. Human parechovirus type 3 was almost invariably found in children less than 4 months of age. In conclusion, a multiplex assay was developed allowing simultaneous detection of 2 viruses, which can cause similar clinical symptoms.


title: Transparenz, Teilhabe und introjektive Identifizierung

text: In this article a transparency of the analyst is seen as a key aspect with respect to the development of the psychoanalytic psychotherapeutic process. Psychoanalysts and psychotherapists with a transparent approach enable their analysands/patients to participate in the course of the analytic work. Transparency and participation jointly facilitate the shared reflection on internal and interactive processes. These processes may take the form of introjective identification. Transparency and participation create an atmosphere in which the dyad has a better grasp of unconscious aspects in the introjective identification. After clarification of the terms transparency and participation and the theoretical background, a case report is presented showcasing crucial interactions in which the mechanism of introjective identification and the internal dramaturgy of both participants is demonstrated. The case report is connected to the theoretical part in the concluding remarks. In the analytic situation the process of introjective identification bridges the gap between the analysand’s and the analyst’s unconscious themes: as a result the psychoanalyst can discover unconscious affects reaching the inner world originally stemming from the unconscious of the analysand/patient. A fertile interplay emerges within the analyst, which can be communicated to the analysand and is then present in the dyadic analytic experience. Transparency and participation are valuable technical means to discover and understand the unconscious part of introjective identification in all its ramifications.


title: Social Vulnerability and Equity: The Disproportionate Impact of COVID‐19

text: As the architect of racial disparity, racism shapes the vulnerability of communities. Socially vulnerable communities are less resilient in their ability to respond to and recover from natural and man‐made disasters when compared to resourced communities. This essay argues that racism exposes existing practices and structures in public administration that, along with the effects of COVID‐19, have led to disproportionate infection and death rates of Black people. Using the Centers for Disease Control's Social Vulnerability Index (SVI) authors analyze the ways Black bodies occupy the most vulnerable communities, making them bear the brunt of COVID‐19’s impact. Findings suggest that existing disparities exacerbate COVID‐19 outcomes for Black people. Targeted universalism is offered as an administrative framework to meet the needs of all people impacted by COVID‐19. This article is protected by copyright. All rights reserved.


title: Update on the target structures of SARS-CoV-2: A systematic review

text: Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of “spike protein,” “main protease/M Pro/3CL pro,” “RNA-dependent RNA polymerase,” and “nonstructural protein 15 Endoribonuclease” of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.


title: Clinical validation of 3 commercial real-time reverse transcriptase polymerase chain reaction assays for the detection of Middle East respiratory syndrome coronavirus from upper respiratory tract specimens

text: Abstract Since discovery of Middle East respiratory syndrome coronavirus (MERS-CoV), a novel betacoronavirus first isolated and characterized in 2012, MERS-CoV real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays represent one of the most rapidly expanding commercial tests. However, in the absence of extensive evaluations of these assays on positive clinical material of different sources, evaluating their diagnostic effectiveness remains challenging. We describe the diagnostic performance evaluation of 3 common commercial MERS-CoV rRT-PCR assays on a large panel (n = 234) of upper respiratory tract specimens collected during an outbreak episode in Saudi Arabia. Assays were compared to the RealStar® MERS-CoV RT-PCR (Alton Diagnostics, Hamburg, Germany) assay as the gold standard. Results showed i) the TIB MolBiol® LightMix UpE and Orf1a assays (TIB MolBiol, Berlin, Germany) to be the most sensitive, followed by ii) the Anyplex™ Seegene MERS-CoV assay (Seegene, Seoul, Korea), and finally iii) the PrimerDesign™ Genesig® HCoV_2012 assay (PrimerDesign, England, United Kingdom). We also evaluate a modified protocol for the PrimerDesign™ Genesig® HCoV_2012 assay.


title: Investigation of sudden death from Mycobacterium tuberculosis in a foreign-born worker at a resort hotel

text: Abstract A 60 year-old man born in Central America died suddenly in the hallway of his residence on the grounds of a resort hotel where he worked as a dishwasher. The dishwashing station was in a large, poorly ventilated area where a substantial number of food service workers (cooks, wait staff, bus persons, dishwashers, supervisors, etc.) shared air space with the index patient. Several social contacts of the patient reported that he had been coughing for many months before his death. The County Department Of Health conducted a contact investigation, which identified 171 individuals in need of follow-up. Thirty-six percent of those tested in the first round were tuberculin skin test-positive; a second round of testing yielded a 15% (8 of 52) conversion rate.


title: Heat inactivation of the Middle East respiratory syndrome coronavirus

text: The culture supernatants of the emerging Middle East respiratory syndrome coronavirus (MERS-CoV) were submitted to three temperatures over time and tested for infectivity by TCID(50) method on Vero E6 cells. At 56°C, almost 25 minutes were necessary to reduce the initial titre by 4 log(10). Increasing temperature to 65°C had a strong negative effect on viral infectivity as virucidy dropped significantly to 1 minute. On the contrary, no significant decrease in titre was observed after 2 hours at 25°C. These data might be useful in establishing biosafety measures in laboratories against MERS-CoV.


title: Identification of COVID-19 can be quicker through artificial intelligence framework using a mobile phone–based survey when cities and towns are under quarantine

text: We propose the use of a machine learning algorithm to improve possible COVID-19 case identification more quickly using a mobile phone–based web survey. This method could reduce the spread of the virus in susceptible populations under quarantine.


title: Obesity as a predictor for a poor prognosis of COVID-19: A systematic review

text: BACKGROUND AND AIMS: COVID-19 is an emerging pandemic due to droplet infection of 2019-novel coronavirus (2019-nCoV). Due to its rapid transmission and high case-fatality rate, recognition of its risk and prognostic factor is important. Obesity has been associated with impaired immune system, increasing the susceptibility for 2019-nCoV infection. We aimed to study the impact of obesity to the prognosis and disease severity of COVID-19. METHODS: A systematic search and handsearching was conducted in four databases: Cochrane, MEDLINE, EMBASE, and PubMed. The identified articles were screened using the chosen eligibility criteria. We obtained three retrospective cohort studies (Wu J et al., Lighter J et al., and Simonnet A et al.) to be critically appraised using Newcastle Ottawa Scale. RESULTS: The findings of all included studies were consistent in stating the contribution of obesity as a risk factor to increase the requirement for advanced medical care. Study with the highest quality, Simonnet A et al., reported an increase need of invasive mechanical ventilation in COVID-19 patients with body mass index higher than 35 kg/m(2), OR: 7.36 (1.63–33.14; p = 0.021). This is associated with a higher mortality rate in obese population infected with COVID-19. CONCLUSION: Obesity is an independent risk and prognostic factor for the disease severity and the requirement of advanced medical care in COVID-19. This systematic review highlights a particularly vulnerable group – obese, and emphasises on the importance of treatment aggression and disease prevention in this population group.


title: Respirators and surgical facemasks for COVID-19: implications for MRI

text: • Respirators used for COVID-19 protection have not been tested for MR safety. • Three of four respirators tested contained ferromagnetic components. • These respirators are ‘MR unsafe’. • Respirators used for COVID-19 protection should be reviewed locally for MR safety. • Surgical masks offer a WHO approved safe alternative for MR staff.


COVID‐19: what is the disaster?


title: In vivo antiviral host response to SARS-CoV-2 by viral load, sex, and age

text: Despite limited genomic diversity, SARS-CoV-2 has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA-sequencing profiles of nasopharyngeal swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with upregulation of antiviral factors such as OAS1-3 and IFIT1-3, and Th1 chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial cultures replicated the in vivo antiviral host response. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of Th1 chemokines CXCL9/10/11 and their cognate receptor, CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B and NK cell-specific transcripts and an increase in inhibitors of NF-κB signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.


title: Ensuring mental health care during the SARS-CoV-2 epidemic in France: a narrative review

text: Abstract Objective: The lack of resources and coordination to face the coronavirus epidemic raises concerns for the health of patients with mental disorders in a country where we still have memories of the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims to propose guidance to ensure mental health care during the SARS-CoV epidemic in France. Methods: The authors performed a narrative review identifying relevant results in the scientific and medical literature and in local initiatives in France. Results: We identified four types of major vulnerabilities among patients with mental disorders during this pandemic: 1) medical comorbidities that are more frequently found among patients with mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which are risk factors for severe covid-19 infection; 2) age (the elderly form the population most vulnerable to the coronavirus); 3) cognitive and behavioural disorders, which can hamper compliance with confinement and hygiene measures and finally and 4) psychosocial vulnerability as a result of stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly suited to psychiatric establishments in a context of major shortages of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds have been closed, wards have high densities of patients, mental health community facilities are closed, and medical teams are understaffed and poorly trained to face infectious diseases. There are also major issues when referring patients with acute mental disorders to intensive care units. To maintain the continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of "COVID+ units". These units are under the dual supervision of a psychiatrist and an internist / infectious disease specialist; all new entrants are placed in quarantine for 14 days; the nursing staff receives specific training, daily medical check-ups and close psychological support. Family visits are prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management are organized with the possibility of home visits, in order to support patients when they get back home and to help them cope with the experience of confinement, which is liable to induce recurrences of mental disorders. The total or partial closure of community mental health facilities is particularly disturbing for patients, but a regular follow-up is possible with telemedicine and should include the monitoring of suicide risk and psycho-education strategies; developing support platforms could also be very helpful in this context. Private practice psychiatrists also have a crucial role of information towards their patients on confinement and barrier measures, and also on measures to prevent the psychological risks inherent in confinement: maintenance of regular sleep r, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. Discussion: French mental healthcare is now facing a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the confinement of the general population.


mTORC inhibitor Sirolimus deprograms monocytes in “cytokine storm” in SARS-CoV2 secondary hemophagocytic lymphohistiocytosis- like syndrome


title: First Complete Genome Sequence of Human Coronavirus HKU1 from a Nonill Bat Guano Miner in Thailand

text: Human coronavirus HKU1 (HCoV-HKU1) was first detected in a patient with viral pneumonia from Hong Kong in 2004. Here, we report the first complete genome sequence of HCoV-HKU1 from Thailand, obtained from a nonill person who worked in a bat cave. Phylogenetic tree analysis revealed it as a group B HCoV-HKU1.


title: Chapter 39 Diseases Involving Myelin

text: The clinical features, pathology, and pathogenesis of the major acquired and inherited diseases involving peripheral and central nervous system myelin are described with an emphasis on the existing knowledge of the neurochemistry relevant to these diseases and areas for future investigation.


title: Viral Infections in Children with Community-Acquired Pneumonia

text: Viral pathogens are commonly isolated from children with community-acquired pneumonia (CAP). Viruses like respiratory syncytial virus, human rhinovirus, human metapneumovirus, parainfluenza viruses, and influenza may act as sole pathogens or may predispose to bacterial pneumonia by a variety of mechanisms. New, emerging, or reemerging viral pathogens occasionally cause outbreaks of severe respiratory tract infection in children. The 2009–2010 H1N1 influenza virus pandemic resulted in increased rates of influenza-related hospitalizations and deaths in children. Rapid viral diagnostic tests based on antigen detection or nucleic acid amplification are increasingly available for clinical use and confirm the importance of viral infection in children hospitalized with CAP. Recently published guidelines for the management of CAP in children note that positive viral test results can modify clinical decision making in children with suspected pneumonia by allowing antibacterial therapy to be withheld in the absence of clinical, laboratory, or radiographic findings that suggest bacterial coinfection.


title: Antimicrobials respond to new threats

text: Plastics Additives & Compounding looks at new developments in the antimicrobial field and how the industry is helping combat some of the world's most virulent diseases.


Radiotherapy imaging: an unexpected ally in fighting COVID 19 pandemic


title: Respiratory virus multiplex RT-PCR assay sensitivities and influence factors in hospitalized children with lower respiratory tract infections

text: Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex II V2.0 kit and explored factors influencing its sensitivity. Nasopharyngeal swab (NPS) specimens were prospectively collected from pediatric inpatients with lower respiratory tract infections at the time of admission in the Shenzhen Children’s Hospital from May 2009 to April 2010. Total nucleic acids were extracted using the EZ1 system (Qiagen, Germany) and 17 respiratory viruses and genotypes including influenza A virus (FluA), FluB, parainfluenza virus 1 (PIV1), PIV2, PIV3, PIV4, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinoviruses (RhV), enteroviruses (EnV), human bocaviruses (hBoV), adenoviruses (AdV), four coronaviruses (229E, OC43, NL63 and HKU1), and FluA 2009 pandemic H1N1(H1N1-p) were detected and identified by the ResPlex II kit. In parallel, 16 real-time TaqMan quantitative RT-PCR assays were used to quantitatively detect each virus except for RhV. Influenza and parainfluenza viral cultures were also performed. Among the total 438 NPS specimens collected during the study period, one or more viral pathogens were detected in 274 (62.6%) and 201(45.9%) specimens by monoplex TaqMan RT-PCR and multiplex ResPlex, respectively. When results from monoplex PCR or cell culture were used as the reference standard, the multiplex PCR possessed specificities of 92.9–100.0%. The sensitivity of multiplex PCR for PIV3, hMPV, PIV1 and BoV were 73.1%, 70%, 66.7% and 55.6%, respectively, while low sensitivities (11.1%–40.0%) were observed for FluA, EnV, OC43, RSV and H1N1. Among the seven viruses/genotypes detected with higher frequencies, multiplex PCR sensitivities were correlated significantly with viral loads determined by the TaqMan RT-PCR in FluA, H1N1-p and RSV (p=0.011−0.000). The Qiagen ResPlex II multiplex RT-PCR kit possesses excellent specificity for simultaneous detection of 17 viral pathogens in NPS specimens in pediatric inpatients at the time of admission. The sensitivity of multiplex RT-PCR was influenced by viral loads, specimen process methods, primer and probe design and amplification condition.


title: Respiratory Virus Pneumonia after Hematopoietic Cell Transplantation: Associations Between Viral Load in Bronchoalveolar Lavage, Viral RNA Detection in Serum, and Transplant Outcomes

text: BACKGROUND: Few data exist regarding respiratory virus quantitation in lower respiratory samples and detection in serum from hematopoietic cell transplantation (HCT) recipients with respiratory virus-associated pneumonia. METHODS: We retrospectively identified HCT recipients with respiratory syncytial virus (RSV), parainfluenza (PIV), influenza, metapneumovirus (MPV), and coronavirus (CoV) detected in BAL samples, and tested stored BAL and/or serum samples using quantitative PCR. RESULTS: In 85 BAL samples from 82 patients, median viral load in copies/ml for RSV (n=35) was 2.6×10(6), PIV (n=35) 4.9×10(7), influenza (n=9) 6.8×10(5), MPV (n=7) 3.9×10(7), and CoV (n=4) 1.8×10(5). Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum of 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A/CoV co-infection (influenza A and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL (p=0.05). Detection of viral RNA in serum was significantly associated with death (adjusted RR 1.8, p=0.02). CONCLUSION: Quantitative PCR detects high viral load in BAL samples from HCT recipients with respiratory virus pneumonia. Viral RNA is also detectable in serum of patients with RSV, influenza, and MPV pneumonia, and may correlate with disease severity.


title: Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases

text: Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis.


title: Learning from a Pandemic

text: The Covid‐19 pandemic has highlighted connections between health and social structural phenomena that have long been recognized in bioethics but have never really been front and center—not just access to health care, but fundamental conditions of living that affect public health, from income inequality to political and environmental conditions. In March, as the pandemic spread globally, the field's traditional focus on health care and health policy, medical research, and biotechnology no longer seemed enough. The adequacy of bioethics seemed even less certain after the killing of George Floyd, whose homicide showed in an especially agonizing way how social institutions are in effect (and often intentionally) designed to make the lives of black people go poorly and end early. Whether bioethics needs to be expanded, redirected, and even reconceived is at the heart of the May‐June 2020 issue of the Hastings Center Report, which is devoted to questions provoked by and lessons emerging during this pandemic.


title: Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

text: MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission.


title: Acute Respiratory Infections in Persons with Spinal Cord Injury

text: Respiratory disorders are the leading cause of death for persons with both acute and chronic spinal cord injury (SCI), and much of the morbidity and mortality associated with respiratory disorders is related to acute respiratory infections. Pneumonia is the best recognized respiratory infection associated with mortality in this population. Recent evidence supports some management strategies that differ from those recommended for the general population. Upper respiratory tract infections and acute bronchitis may be precipitating factors in the development of pneumonia or ventilatory failure in patients with chronic SCI. This review emphasizes management principles for treatment and prevention of respiratory infections in persons with SCI.


title: Concordancia entre dos pruebas de detección rápida para la detección de anticuerpos contra el SARS-CoV-2

text: Objective: To assess the agreement between two rapid detection tests (RDT) for antibodies against SARS-CoV-2 infection. Materials and methods: This was a cross-sectional study that used a random sample of non-hospitalized patients from the primary care management division of the Healthcare Area of Leon (58 RT-PCR-positive cases and 52 RT-PCR-negative cases). Information regarding symptoms was collected and all patients were simultaneously tested using two RDTs (Combined - cRDT and Differentiated - dRDT). The results of both tests were evaluated using the chi-square test and, for degree of agreement, the kappa coefficient. Results: About 52% of the participants were women (mean age: 48.2 ± 11.0 years). A total of 58.2% were positive for d-RDT and 41.2% were positive for c-RDT. In the subjects who were RT-PCR-positive, d-RDT was positive in 72.4% and c-RDT in 55.2%; in those who were RT-PCR-negative, the percentages were 42.3% and 26.9%, respectively. The kappa coefficient observed between the two RDTs was 0.644, and was higher in patients without a fever or anosmia (0.725) and lower in those with a fever or anosmia (0.524). Conclusions: There is good agreement between the tests used in this study. Given the sensitivity observed, they can be very useful as a complement to RT-PCR.


title: Southeast Asian cooperation in health: a comparative perspective on regional health governance in ASEAN and the EU

text: Globalization has led to new health challenges for the twenty-first century. These new health challenges have transnational implications and involve a large range of actors and stakeholders. National governments no longer hold the sole responsibility for the health of their people. These changes in health trends have led to the rise of global health governance as a theoretical notion for health policy making. The Southeast Asian region is particularly prone to public health threats such as emerging infectious diseases and faces future health challenges including those of noncommunicable diseases. This study looks at the potential of the Association of Southeast Asian Nations (ASEAN) as a regional organization to lead a regional dynamic for health cooperation in order to overcome these challenges. Through a comparative study with the regional mechanisms of the European Union (EU) for health cooperation, we look at how ASEAN could maximize its potential as a global health actor. Our study is based on primary research and semistructured field interviews. To illustrate our arguments, we refer to the extent of regional cooperation for health in ASEAN and the EU for (re)emerging infectious disease control and for tobacco control. We argue that regional institutions and a network of civil society organizations are crucial in relaying global initiatives, and ensuring the effective implementation of global guidelines at the national level. ASEAN’s role as a regional body for health governance will depend both on greater horizontal and vertical integration through enhanced regional mechanisms and a wider matrix of cooperation.


title: Response to “uncertainties on the prognostic value of D‐dimers in COVID‐19 patients”

text: We appreciate the opportunity to respond to the letter from Dr Gris and colleagues. It is true there were several limitations in our study. However, we still believe that D‐dimer level at admission could be an effective and easily available predictor in patients with coronavirus disease 2019 (COVID‐19).


title: SARS, a shipwreck, a NATO attack, and September 11, 2001: Global information flows and Chinese responses to tragic news events

text: In this article, I examine how Chinese citizens in China and abroad used discourses of Chinese backwardness to make sense of tragic news events while simultaneously trying to avoid becoming identified with that backwardness. I focus on various interpretations of NATO's bombing of the Chinese embassy in Belgrade in 1999; the September 11, 2001, terrorist attacks; the sinking of a Chinese ferry in 1999; and the 2003 severe acute respiratory syndrome (SARS) epidemic to explore how Chinese citizens negotiated between their own ambivalent loyalties and the contradictory official, unofficial, local, national, and international narratives in which these events were embedded. These negotiations suggest that global information flows are creating a transnational panopticon that increasingly enables neoliberal governmentality to operate on transnational levels.


title: #SendHelpNow: Mental wellness and virtual connection in the age of coronavirus

text: Coronavirus, coronavirus disease (COVID‐19) and social/physical distancing are among the words that have become household names amidst this pandemic. Not only has our vocabulary changed, but also the ways we connect with others. We have become even more reliant on technological advances for business, education, pleasure and other activities. In fact, 93% of Americans report that an outage in internet or cellular service during the outbreak would cause problems in their daily lives (Pew Research Center, 2020).


title: A current update on the phytopharmacological aspects of Houttuynia cordata Thunb

text: The present review is an attempt to put an insight into a medicinal plant Houttuynia cordata Thunb, which is indigenous to North-East India and China. It is an aromatic medicinal herb belonging to family Saururaceae and is restricted to specialized moist habitats. The review provides detailed information regarding the morphology, distribution, phytochemistry, ethnopharmacological uses and also describes various pharmacological activities reported on the plant H. cordata. The review describes therapeutic efficacy of the whole plant and its extracts, fractions and isolated compounds in different diseased condition. Among the important pharmacological activities reported includes, anti-mutagenic, anti-cancer, adjuvanticity, anti-obesity, hepatoprotective, anti-viral, anti-bacterial, anti-inflammatory, free radical scavenging, anti-microbial, anti-allergic, anti-leukemic, chronic sinusitis and nasal polyps activities. Thus, the present review will act as a source of referential information to researchers to perform clinical studies on isolated compounds that may serve the society and will help in improving human health care system.


title: Extreme events and emergency scales()

text: An event is extreme if its magnitude exceeds the threshold. A choice of a threshold is subject to uncertainty caused by a method, the size of available data, a hypothesis on statistics, etc. We assess the degree of uncertainty by the Shannon’s entropy calculated on the probability that the threshold changes at any given time. If the amount of data is not sufficient, an observer is in the state of Lewis Carroll’s Red Queen who said “When you say hill, I could show you hills, in comparison with which you’d call that a valley”. If we have enough data, the uncertainty curve peaks at two values clearly separating the magnitudes of events into three emergency scales: subcritical, critical, and extreme. Our approach to defining the emergency scale is validated by 39 years of Standard and Poor’s 500 (S&P500) historical data.


title: Evolution of selective-sequencing approaches for virus discovery and virome analysis

text: Abstract Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for the study of viromes, sample preparation methodologies use different approaches to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focus on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density gradient centrifugation. However, recently a new approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was developed to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we discuss the different methods, their applications and evolution, for selective sequencing based virome analysis and also propose refinements needed to harness the full potential of HTS for virome analysis.


title: Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study

text: BACKGROUND: Multiplex real-time polymerase chain reaction assays have improved diagnostic sensitivity for a wide range of pathogens. However, co-detection of multiple agents and bacterial colonization make it difficult to distinguish between asymptomatic infection or illness aetiology. We assessed whether semi-quantitative microbial load data can differentiate between symptomatic and asymptomatic states for common respiratory pathogens. METHODS: We obtained throat and nasal swab samples from military trainees at two Thai Army barracks. Specimens were collected at the start and end of 10-week training periods (non-acute samples), and from individuals who developed upper respiratory tract infection during training (acute samples). We analysed the samples using a commercial multiplex respiratory panel comprising 33 bacterial, viral and fungal targets. We used random effects tobit models to compare cycle threshold (Ct) value distributions from non-acute and acute samples. RESULTS: We analysed 341 non-acute and 145 acute swab samples from 274 participants. Haemophilus influenzae type B was the most commonly detected microbe (77.4% of non-acute and 64.8% of acute samples). In acute samples, nine specific microbe pairs were detected more frequently than expected by chance. Regression models indicated significantly lower microbial load in non-acute relative to acute samples for H. influenzae non-type B, Streptococcus pneumoniae and rhinovirus, although it was not possible to identify a Ct-value threshold indicating causal etiology for any of these organisms. CONCLUSIONS: Semi-quantitative measures of microbial concentration did not reliably differentiate between illness and asymptomatic colonization, suggesting that clinical symptoms may not always be directly related to microbial load for common respiratory infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3358-4) contains supplementary material, which is available to authorized users.


title: Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19

text: [Image: see text] The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action—to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir’s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.


title: Challenges of managing the asymptomatic carriers of SARS-CoV-2

text: Abstract After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States.Presently, the World Health Organization indicates that fatality due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARSCoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established.In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention or being diagnosed as carriers. Thus, managing the asymptomatic cases, who can carry and likely transmit the virus, is a major healthcare challenge while a pandemic is looming.


title: Plant made anti-HIV microbicides—A field of opportunity

text: Abstract HIV remains a significant global burden and without an effective vaccine, it is crucial to develop microbicides to halt the initial transmission of the virus. Several microbicides have been researched with various levels of success. Amongst these, the broadly neutralising antibodies and peptide lectins are promising in that they can immediately act on the virus and have proven efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate molecules, it appears that current production systems are overburdened and expensive to establish and maintain. With recent developments in vector systems for protein expression coupled with downstream protein purification technologies, plants are rapidly gaining credibility as alternative production systems. Here we evaluate the advances made in host and vector system development for plant expression as well as the progress made in expressing HIV neutralising antibodies and peptide lectins using plant-based platforms.


title: Which Kind of Provider’s Operation Volumes Matters? Associations between CABG Surgical Site Infection Risk and Hospital and Surgeon Operation Volumes among Medical Centers in Taiwan

text: BACKGROUND: Volume-infection relationships have been examined for high-risk surgical procedures, but the conclusions remain controversial. The inconsistency might be due to inaccurate identification of cases of infection and different methods of categorizing service volumes. This study takes coronary artery bypass graft (CABG) surgical site infections (SSIs) as an example to examine whether a relationship exists between operation volumes and SSIs, when different SSIs case identification, definitions and categorization methods of operation volumes were implemented. METHODS: A population-based cross-sectional multilevel study was conducted. A total of 7,007 patients who received CABG surgery between 2006 and 2008 from19 medical centers in Taiwan were recruited. SSIs associated with CABG surgery were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) codes and a Classification and Regression Trees (CART) model. Two definitions of surgeon and hospital operation volumes were used: (1) the cumulative CABG operation volumes within the study period; and (2) the cumulative CABG operation volumes in the previous one year before each CABG surgery. Operation volumes were further treated in three different ways: (1) a continuous variable; (2) a categorical variable based on the quartile; and (3) a data-driven categorical variable based on k-means clustering algorithm. Furthermore, subgroup analysis for comorbidities was also conducted. RESULTS: This study showed that hospital volumes were not significantly associated with SSIs, no matter which definitions or categorization methods of operation volume, or SSIs case identification approaches were used. On the contrary, the relationships between surgeon’s volumes varied. Most of the models demonstrated that the low-volume surgeons had higher risk than high-volume surgeons. CONCLUSION: Surgeon volumes were more important than hospital volumes in exploring the relationship between CABG operation volumes and SSIs in Taiwan. However, the relationships were not robust. Definitions and categorization methods of operation volume and correct identification of SSIs are important issues for future research.


title: Solid‐phase synthesis and screening of a library of C‐terminal arginine peptide aldehydes against Murray Valley encephalitis virus protease

text: Murray Valley encephalitis virus is a member of the flavivirus group, a large family of single‐stranded RNA viruses, which cause serious disease in all regions of the world. Unfortunately, no suitable antivirals are available, and there are commercial vaccines for only three flaviviruses. The solid‐phase synthesis of a library of 400 C‐terminal arginine peptide aldehydes and their screening against Murray Valley encephalitis virus protease are demonstrated. The library was utilised to elucidate several tripeptide sequences that can be used as inhibitors in further SAR studies. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.


Preparing medical students for global challenges beyond COVID‐19


title: The PRRSV replicase: Exploring the multifunctionality of an intriguing set of nonstructural proteins

text: Abstract Our knowledge about the structure and function of the nonstructural proteins (nsps) encoded by the arterivirus replicase gene has advanced in recent years. The continued characterization of the nsps of the arterivirus prototype equine arteritis virus has not only corroborated several important functional predictions, but also revealed various novel features of arteriviral replication. For porcine reproductive and respiratory syndrome virus (PRRSV), based on bioinformatics predictions and experimental studies, a processing map for the pp1a and pp1ab replicase polyproteins has been developed. Crystal structures have been resolved for two of the PRRSV nonstructural proteins that possess proteinase activity (nsp1α and nsp4). The functional characterization of the key enzymes for arterivirus RNA synthesis, the nsp9 RNA polymerase and nsp10 helicase, has been initiated. In addition, progress has been made on nsp functions relating to the regulation of subgenomic mRNAs synthesis (nsp1), the induction of replication-associated membrane rearrangements (nsp2 and nsp3), and an intriguing replicative endoribonuclease (nsp11) for which the natural substrate remains to be identified. The role of nsps in viral pathogenesis and host immunity is also being explored, and specific nsps (including nsp1α/β, nsp2, nsp4, nsp7, and nsp11) have been implicated in the modulation of host immune responses to PRRSV infection. The nsp3–8 region was identified as containing major virulence factors, although mechanistic information is scarce. The biological significance of PRRSV nsps in virus-host interactions and the technical advancements in engineering the PRRSV genome by reverse genetics are also reflected in recent developments in the area of vaccines and diagnostic assays.


title: Using serology to anticipate measles post-honeymoon period outbreaks

text: Abstract Measles vaccination is a public health ‘best buy’, with the highest cost of illness averted of any vaccine-preventable disease [1]. In the last decades, substantial reductions have been made in the number of measles cases, with an estimated 20 million deaths averted from 2000 to 2017 [2]. Yet, an important feature of epidemic dynamics is that large outbreaks can occur following years of apparently successful control [3]. Such ‘post-honeymoon period’ outbreaks are a result of the non-linear dynamics of epidemics [3]. Anticipating post-honeymoon outbreaks could lead to substantial gains in public health, helping to guide the timing, age-range and location of catch-up vaccination campaigns [4]. Theoretical conditions for such outbreaks are well-understood for measles, yet the information required to make these calculations policy-relevant is largely lacking. We propose that a major extension of serological studies to directly characterize measles susceptibility is a high priority.


title: Three key proteases – angiotensin-I-converting enzyme (ACE), ACE2 and renin – within and beyond the renin-angiotensin system

text: Summary The discovery of angiotensin-I-converting enzyme 2 (ACE2) and a (pro)renin receptor has renewed interest in the physiology of the renin-angiotensin system (RAS). Through the ACE2/angiotensin-(1–7)/Mas counter-regulatory axis, ACE2 balances the vasoconstrictive, proliferative, fibrotic and proinflammatory effects of the ACE/angiotensin II/AT1 axis. The (pro)renin receptor system shows an angiotensin-dependent function related to increased generation of angiotensin I, and an angiotensin-independent aspect related to intracellular signalling. Activation of ACE2 and inhibition of ACE and renin have been at the core of the RAS regulation. The aim of this review is to discuss the biochemistry and biological functions of ACE, ACE2 and renin within and beyond the RAS, and thus provide a perspective for future bioactives from natural plant and/or food resources related to the three proteases.


title: The central role of Fas‐ligand cell signaling in inflammatory lung diseases

text: Following inflammation and injury in the lung, loss of epithelial cell precursors could determine the balance between tissue regeneration and fibrosis. This review discusses evidence that proapoptotic Fas‐Fas ligand (FasL) signaling plays a central role in pulmonary inflammation, injury and fibrosis. FasL signaling induces inflammatory apoptosis in epithelial cells and alveolar macrophages, with concomitant IL‐1β and chemokine release, leading to neutrophil infiltration. FasL signaling plays a critical role in models of acute lung injury, idiopathic pulmonary fibrosis and silicosis; blockade of Fas‐FasL interactions either prevents or attenuates pulmonary inflammation and fibrosis. Serologic and immunohistochemical studies in patients support a major pathogenic role of Fas and FasL molecules in inflammatory lung diseases. Identification of the pathogenic role of FasL could facilitate the discovery of more effective treatments for currently untreatable inflammatory lung diseases.


title: Influence of Dendritic Cells on Viral Pathogenicity

text: Although most viral infections cause minor, if any, symptoms, a certain number result in serious illness. Viral disease symptoms result both from direct viral replication within host cells and from indirect immunopathological consequences. Dendritic cells (DCs) are key determinants of viral disease outcome; they activate immune responses during viral infection and direct T cells toward distinct T helper type responses. Certain viruses are able to skew cytokine secretion by DCs inducing and/or downregulating the immune system with the aim of facilitating and prolonging release of progeny. Thus, the interaction of DCs with viruses most often results in the absence of disease or complete recovery when natural functions of DCs prevail, but may lead to chronic illness or death when these functions are outmanoeuvred by viruses in the exploitation of DCs.