title: Concurrent purification of two defense proteins from French bean seeds: a defensin‐like antifungal peptide and a hemagglutinin

text: A purification protocol is described herein for concurrent isolation of two defense proteins including a 6‐kDa defensin‐like antifungal peptide and a 60‐kDa dimeric hemagglutinin from seeds of the French bean (Phaseolus vulgaris). It involved ion‐exchange chromatography on SP‐Sepharose, affinity chromatography on Affi‐gel blue gel, ion‐exchange chromatography on Q‐Sepharose, and gel filtration on Superdex Peptide (for defensin‐like antifungal peptide) or Superdex 200 (for hemagglutinin). Both antifungal and hemagglutinating activities were adsorbed on SP‐Sepharose and then on Affi‐gel blue gel. Hemagglutinin was subsequently unadsorbed and defensin‐like antifungal peptide adsorbed on Q‐Sepharose. The antifungal activity of the antifungal peptide was stable in the temperature range of 0–90 °C for 20 min, in the pH range of 4–10, and after exposure to trypsin (1 mg/ml) at 37 °C for 1 h. The hemagglutinin was stable from 10 to 80 °C, from pH 1 to 12, and after treatment with trypsin at 37 °C for 2 h. It inhibited [methyl‐(3)H]thymidine incorporation into breast cancer (MCF‐7), leukemia (L1210), hepatoma (HepG2) and human embryonic liver (WRL68) cells with an IC(50) of 6.6, 7, 13 and 15 µm, respectively, and elicited maximal mitogenic response from mouse splenocytes at 1 µm concentration. It curtailed HIV‐1 reverse transcriptase activity with an IC(50) of 1.9 µm, but was devoid of antifungal activity. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.


title: Microarray for Identification of the Chiropteran Host Species of Rabies Virus in Canada

text: Species identification through genetic barcoding can augment traditional taxonomic methods, which rely on morphological features of the specimen. Such approaches are especially valuable when specimens are in poor condition or comprise very limited material, a situation that often applies to chiropteran (bat) specimens submitted to the Canadian Food Inspection Agency for rabies diagnosis. Coupled with phenotypic plasticity of many species and inconclusive taxonomic keys, species identification using only morphological traits can be challenging. In this study, a microarray assay with associated PCR of the mitochondrial cytochrome c oxidase subunit I (COI) gene was developed for differentiation of 14 bat species submitted to the Canadian Food Inspection Agency from 1985–2012 for rabies diagnosis. The assay was validated with a reference collection of DNA from 153 field samples, all of which had been barcoded previously. The COI gene from 152 samples which included multiple specimens of each target species were successfully amplified by PCR and accurately identified by the microarray. One sample that was severely decomposed failed to amplify with PCR primers developed in this study, but amplified weakly after switching to alternate primers and was accurately typed by the microarray. Thus, the chiropteran microarray was able to accurately differentiate between the 14 species of Canadian bats targeted. This PCR and microarray assay would allow unequivocal identification to species of most, if not all, bat specimens submitted for rabies diagnosis in Canada.


title: Phylogenetic and recombination analysis of Tobacco bushy top virus in China

text: BACKGROUND: During the past decade, tobacco bushy top disease, which is mainly caused by a combination of Tobacco bushy top virus (TBTV) and Tobacco vein-distorting virus (TVDV), underwent a sudden appearance, extreme virulence and degeneration of the epidemic in the Yunnan province of China. In addition to integrative control of its aphid vector, it is of interest to examine diversity and evolution among different TBTV isolates. METHODS: 5’ and 3’ RACE, combined with one step full-length RT-PCR, were used to clone the full-length genome of three new isolates of TBTV that exhibited mild pathogenicity in Chinese fields. Nucleotide and amino acid sequences for the TBTV isolates were analyzed by DNAMAN. MEGA 5.0 was used to construct phylogenetic trees. RDP4 was used to detect recombination events during evolution of these isolates. RESULTS: The genomes of three isolates, termed TBTV-JC, TBTV-MD-I and TBTV-MD-II, were 4152 nt in length and included one distinctive difference from previously reported TBTV isolates: the first nucleotide of the genome was a guanylate instead of an adenylate. Diversity and phylogenetic analyses among these three new TBTV isolates and five other available isolates suggest that ORFs and 3’UTRs of TBTV may have evolved separately. Moreover, the RdRp-coding region was the most variable. Recombination analysis detected a total of 29 recombination events in the 8 TBTV isolates, in which 24 events are highly likely and 5 events have low-level likelihood based on their correlation with the phylogenetic trees. The three new TBTV isolates have individual recombination patterns with subtle divergences in parents and locations. CONCLUSIONS: The genome sizes of TBTV isolates were constant while different ORF-coding regions and 3’UTRs may have evolved separately. The RdRp-coding region was the most variable. Frequent recombination occurred among TBTV isolates. Three new TBTV isolates have individual recombination patterns and may have different progenitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0340-2) contains supplementary material, which is available to authorized users.


title: Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Type I Interferon Signaling by Targeting IRF9

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus from the Nidovirales order that causes reproductive failure and respiratory disease in pigs and poses a constant threat to the global pig industry. The PRRSV-encoded nonstructural protein 11 (nsp11) is a nidovirus-specific endoribonuclease (NendoU) that is conserved throughout the Arteriviridae and Coronaviridae families. Previously, our research and that of others demonstrated that PRRSV nsp11 inhibits type I interferon (IFN) production through NendoU activity-dependent mechanisms. Here, we found that PRRSV nsp11 also inhibited IFN-stimulated response element (ISRE) promoter activity and subsequent transcription of IFN-stimulated genes (ISGs). Detailed analysis showed that nsp11 targeted interferon regulatory factor 9 (IRF9), but not transducer and activator of transcription 1 (STAT1) or STAT2, key molecules in the type I IFN signaling pathway. Furthermore, the nsp11-IRF9 interaction impaired the formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) in both nsp11-overexpressed and PRRSV-infected cells. Importantly, nsp11 mutations (H129A, H144A, and K173A) that ablate NendoU activity or its cell cytotoxicity also interacted with IRF9 and retained the ability to block IFN signaling, indicating that the nsp11-IRF9 interaction is independent of NendoU activity or cell cytotoxicity of nsp11. Taking the results together, our study demonstrated that PRRSV nsp11 antagonizes type I IFN signaling by targeting IRF9 via a NendoU activity-independent mechanism, and this report describes a novel strategy evolved by PRRSV to counteract host innate antiviral responses, revealing a potential new function for PRRSV nsp11 in type I IFN signaling. IMPORTANCE The nidovirus-specific endoribonuclease (NendoU) encoded by PRRSV nonstructural protein 11 (nsp11) is a unique NendoU of nidoviruses that infect vertebrates; thus, it is an attractive target for the development of antinidovirus drugs. Previous studies have revealed that the NendoU of nidoviruses, including porcine reproductive and respiratory syndrome virus (PRRSV) and human coronavirus 229E (HCoV-229E), acts as a type I interferon (IFN) antagonist. Here, for the first time, we demonstrated that overexpression of PRRSV nsp11 also inhibits IFN signaling by targeting the C-terminal interferon regulatory factor (IRF) association domain of IRF9. This interaction impaired the ability of IRF9 to form the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) and to act as a signaling protein of IFN signaling. Collectively, our data identify IRF9 as a natural target of PRRSV NendoU and reveal a novel mechanism evolved by an arterivirus to counteract innate immune signaling.


title: Medical and Paramedical Care of Patients With Cerebellar Ataxia During the COVID-19 Outbreak: Seven Practical Recommendations of the COVID 19 Cerebellum Task Force

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic.


title: Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

text: BACKGROUND: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. METHODS: During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies. FINDINGS: The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years. INTERPRETATION: To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. FUNDING: None.


title: Nigeria and Italy Divergences in Coronavirus Experience: Impact of Population Density

text: BACKGROUND: The reports and information on coronavirus are not conspicuously emphasising the possible impact of population density on the explanation of difference in rapid spread and fatality due to the disease and not much has been done on bicountry comparisons. OBJECTIVE: The study examined the impact of population density on the spread of COVID-19 pandemic in two sociodemographic divergent countries. METHODS: The study conducted a scoping review of published and unpublished articles including blogs on incidences and fatalities of COVID-19. The analysis followed qualitative description and quantitative presentation of the findings using only frequency distribution, percentages, and graphs. RESULTS: The two countries shared similar experience of “importation” of COVID-19, but while different states ordered partial lockdown in Nigeria, it was an immediate total lockdown in Italy. The physician/patient ratio is high in Italy (1 : 328) but low in Nigeria (1 : 2500), while population density is 221 in Nigeria and 206 in Italy. Daily change in incidence rate reduced to below 20% after 51 and 30 days of COVID-19 first incidence in Italy and Nigeria, respectively. Fatality rate has plummeted to below 10% after the 66(th) day in Italy but has not been stabilised in Nigeria. CONCLUSION: The authors upheld both governments' recommending measures that tilted towards personal hand-hygienic practices and social distancing. Authors suggested that if Italy with its high physician/patient ratio and lower population density compared to Nigeria could suffer high fatality from COVID-19 pandemic under four weeks, then Nigeria with its low physician/patient ratio and higher population density should prepare to face harder time if the pandemic persists.


title: Academic Emergency Medicine Physicians’ Anxiety Levels, Stressors and Potential Stress Mitigation Measures during the Acceleration Phase of the COVID‐19 Pandemic

text: OBJECTIVE: To assess anxiety and burnout levels, home life changes and measures to relieve stress of United States academic emergency medicine (EM) physicians during the COVID‐19 pandemic acceleration phase. METHODS: We sent a cross‐sectional email survey to all EM physicians at seven academic emergency departments. The survey incorporated items from validated stress scales and assessed perceptions and key elements in the following domains: numbers of suspected COVID‐19 patients, availability of diagnostic testing, levels of home and workplace anxiety, severity of work burnout, identification of stressors, changes in home behaviors, and measures to decrease provider anxiety. RESULTS: 426 (56.7%) EM physicians responded. On a scale of 1‐7 (1= not at all, 4 = somewhat, and 7=extremely), the median (interquartile range) reported effect of the pandemic on both work and home stress levels was 5 (4,6). Reported levels of emotional exhaustion/burnout increased from pre‐pandemic median 3 (2,4) to since the pandemic started median 4 (3,6); difference in medians = 1.8 (95% confidence interval 1.7‐1.9). Most physicians (90.8%) reported changing their behavior towards family and friends, especially by decreasing signs of affection (76.8%). The most commonly cited measures cited to alleviate stress/anxiety were increasing personal protective equipment availability (PPE), offering rapid COVID‐19 testing at physician discretion, providing clearer communication about COVID‐19 protocol changes, and assuring that physicians can take leave for care of family and self. CONCLUSIONS: During the acceleration phase, the COVID‐19 pandemic has induced substantial workplace and home anxiety in academic EM physicians and their exposure during work has had a major impact on their home lives. Measures cited to decrease stress include enhanced availability of PPE, rapid turnaround testing at provider discretion, and clear communication about COVID‐19 protocol changes.


title: CVD Polymers for Devices and Device Fabrication

text: Chemical vapor deposition (CVD) polymerization directly synthesizes organic thin films on a substrate from vapor phase reactants. Dielectric, semiconducting, electrically conducting, and ionically conducting CVD polymers have all been readily integrated into devices. The absence of solvent in the CVD process enables the growth of high‐purity layers and avoids the potential of dewetting phenomena, which lead to pinhole defects. By limiting contaminants and defects, ultrathin (<10 nm) CVD polymeric device layers have been fabricated in multiple laboratories. The CVD method is particularly suitable for synthesizing insoluble conductive polymers, layers with high densities of organic functional groups, and robust crosslinked networks. Additionally, CVD polymers are prized for the ability to conformally cover rough surfaces, like those of paper and textile substrates, as well as the complex geometries of micro‐ and nanostructured devices. By employing low processing temperatures, CVD polymerization avoids damaging substrates and underlying device layers. This report discusses the mechanisms of the major CVD polymerization techniques and the recent progress of their applications in devices and device fabrication, with emphasis on initiated CVD (iCVD) and oxidative CVD (oCVD) polymerization.


title: Coronavirus comes home? Energy use, home energy management, and the social-psychological factors of COVID-19

text: This study explores energy use patterns, climate change issues, and the relationship between social-psychological factors, and residents’ acceptance of and willingness to pay (WTP) for home energy management systems (HEMS) during COVID-19 pandemic in New York. The results of our survey suggest that there were no longer morning or evening usage peaks on weekdays during COVID-19. A significant portion of respondents is experiencing higher or much higher electricity use than average. Most residents perceived climate change issues during COVID-19 being about the same as before. Attitude perceived behavioral control and social norms are overall the strongest predictors of adoption intention and WTP. Regarding WTP for specific well-being features, attitude was the strongest positive predictor of telemedical and home security, and social norms are the strongest positive predictor of elderly assistance and job search. Technology anxiety, surprisingly, positively influence WTP for well-being features. Trust in utilities is not related to adoption intention, but is positively associated with WTP for the well-being features. Although cybersecurity concern is positively related to HEMS adoption intention for energy and well-being features, this relationship is not significant in WTP. Residents who had a moderate level of the perceived risk of getting infected by COVID-19 are willing to pay more than the high- and low-risk groups. This paper addresses the multi-dimensionality by focusing on the interaction among technology attributes such as energy and well-being features, and users’ social-psychological and demographics factors. This study provides insights for further research in examining similar topics relating to COVID-19 energy issues.


title: Helping medical educators world‐wide pivot their curricula online: PivotMedEd.com

text: The COVID‐19 pandemic resulted in many countries implementing restrictions on group gatherings and educational events, creating imperatives for educators to move curricula online with short notice. Within medical schools and health sciences programs, this urgency was compounded by competing priorities of healthcare delivery, since many educators were also clinicians.


title: What we know but do not understand about nidovirus helicases

text: Abstract Helicases are versatile NTP-dependent motor proteins of monophyletic origin that are found in all kingdoms of life. Their functions range from nucleic acid duplex unwinding to protein displacement and double-strand translocation. This explains their participation in virtually every metabolic process that involves nucleic acids, including DNA replication, recombination and repair, transcription, translation, as well as RNA processing. Helicases are encoded by all plant and animal viruses with a positive-sense RNA genome that is larger than 7kb, indicating a link to genome size evolution in this virus class. Viral helicases belong to three out of the six currently recognized superfamilies, SF1, SF2, and SF3. Despite being omnipresent, highly conserved and essential, only a few viral helicases, mostly from SF2, have been studied extensively. In general, their specific roles in the viral replication cycle remain poorly understood at present. The SF1 helicase protein of viruses classified in the order Nidovirales is encoded in replicase open reading frame 1b (ORF1b), which is translated to give rise to a large polyprotein following a ribosomal frameshift from the upstream ORF1a. Proteolytic processing of the replicase polyprotein yields a dozen or so mature proteins, one of which includes a helicase. Its hallmark is the presence of an N-terminal multi-nuclear zinc-binding domain, the nidoviral genetic marker and one of the most conserved domains across members of the order. This review summarizes biochemical, structural, and genetic data, including drug development studies, obtained using helicases originating from several mammalian nidoviruses, along with the results of the genomics characterization of a much larger number of (putative) helicases of vertebrate and invertebrate nidoviruses. In the context of our knowledge of related helicases of cellular and viral origin, it discusses the implications of these results for the protein's emerging critical function(s) in nidovirus evolution, genome replication and expression, virion biogenesis, and possibly also post-transcriptional processing of viral RNAs. Using our accumulated knowledge and highlighting gaps in our data, concepts and approaches, it concludes with a perspective on future research aimed at elucidating the role of helicases in the nidovirus replication cycle.


title: Evidence for RNA editing in the transcriptome of 2019 Novel Coronavirus

text: The 2019-nCoV outbreak has become a global health risk. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from two Wuhan patients. We identify nucleotide changes that may be signatures of RNA editing: Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals patterns similar to the RNA editing pattern observed in the 2019-nCoV transcriptomes. Our results suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient.


title: Research Designs and Methodologies Related to Pharmacy Practice

text: Abstract The need for evidence to inform policy and practice in pharmacy is becoming increasingly important. In parallel, clinical pharmacy and practice research is evolving. Research evidence should be used to identify new areas for improved health service delivery and rigorously evaluate new services in pharmacy. The generation of such evidence through practice-based research should be predicated on appropriate use of robust and rigorous methodologies. In addition to the quantitative and qualitative approaches used in pharmacy practice research, mixed methods and other novel approaches are increasingly being applied in pharmacy practice research. Approaches such as discrete choice experiments, Delphi techniques, and simulated client technique are now commonly used in pharmacy practice research. Therefore, pharmacy practice researchers need to be competent in the selection, application, and interpretation of these methodological and analytical approaches. This chapter focuses on introducing traditional and novel study designs and methodologies that are particularly pertinent to contemporary clinical pharmacy and practice research. This chapter will introduce the fundamentals and structures of these methodologies, but more details regarding the different approaches may be found within the Encyclopedia.


title: Cross-sectional IgM and IgG profiles in SARS-CoV-2 infection

text: BACKGROUND: Accurate serological assays can improve the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but few studies have compared performance characteristics between assays in symptomatic and recovered patients. METHODS: We recruited 32 patients who had 2019 coronavirus disease (COVID-19; 18 hospitalized and actively symptomatic, 14 recovered mild cases), and measured levels of IgM (against the full-length S1 or the highly homologous SARS-CoV E protein) and IgG (against S1 receptor binding domain [RBD]). We performed the same analysis in 103 pre-2020 healthy adult control (HC) participants and 13 participants who had negative molecular testing for SARS-CoV-2. RESULTS: Anti-S1-RBD IgG levels were very elevated within days of symptom onset for hospitalized patients (median 2.04 optical density [OD], vs. 0.12 in HC). People who recovered from milder COVID-19 only reached similar IgG levels 28 days after symptom onset. IgM levels were elevated early in both groups (median 1.91 and 2.12 vs. 1.14 OD in HC for anti-S1 IgM, 2.23 and 2.26 vs 1.52 in HC for anti-E IgM), with downward trends in hospitalized cases having longer disease duration. The combination of the two IgM levels showed similar sensitivity for COVID-19 as IgG but greater specificity, and identified 4/10 people (vs. 3/10 by IgG) with prior symptoms and negative molecular testing to have had COVID-19. CONCLUSIONS: Disease severity and timing both influence levels of IgM and IgG against SARS-CoV-2, with IgG better for early detection of severe cases but IgM more suited for early detection of milder cases.


title: Progress in public health risk communication in China: lessons learned from SARS to H7N9

text: BACKGROUND: Following the SARS outbreak, the World Health Organization revised the International Health Regulations to include risk communication as one of the core capacity areas. In 2006, the U.S. Centers for Disease Control and Prevention’s Global Disease Detection [GDD] program began collaborating with China to enhance China’s risk communication capacity to address gaps in the SARS communication response. This article describes tangible improvements in China’s public health emergency risk communication capacity between the SARS and H7N9 outbreaks; documents U.S. CDC GDD cooperative technical assistance during 2006–2017; and shares lessons learnt to benefit other countries and contribute to enhance global health security. METHOD: A questionnaire based on the WHO Joint External Evaluation tool [Risk Communication section] was developed. A key communications official from the China National Health Commission [NHC] completed the questionnaire retrospectively to reflect China’s capacity to manage communication response before, during and after the outbreaks of SARS in 2003, influenza H1N1 in 2009, and influenza H7N9 in 2013. A literature search was also conducted in English and Chinese to further substantiate the results of the questionnaire completed by NHC. RESULTS: China demonstrated significantly improved risk communication capacities of pre-event, during event and post event responses to H7N9 when compared to the SARS response. China NHC improved its response through preparedness, availability of dedicated staff and resources for risk communication, internal clearance mechanisms, standard operating procedures with national response parties external to NHC, rumor management, communication with international agencies and consistent messaging with healthcare and private sectors. Correspondingly, the perceived level of trust that the public had in the NHC following outbreaks rose between the SARS and H7N9 response. CONCLUSION: Risk communication capacities in China have increased during the ten years between the SARS outbreak of 2003 and the H7N9 outbreak of 2013. Long-term risk communication capacity building efforts in bilateral collaborations are uncommon. The U.S. CDC GDD project was one of the first such collaborations worldwide. The lessons learned from this project may benefit lower and middle-income countries as they build their national emergency risk communication capacity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6778-1) contains supplementary material, which is available to authorized users.


Safeguarding against Ebola: Vaccines and therapeutics to be stockpiled for future outbreaks


title: Provider perspectives on general practice in Henan, China: a mixed-methods study

text: OBJECTIVE: Since 2011 China’s central government has committed to establishing a new ‘general practitioner’ (GP)-centred primary care system. To this end there have been great efforts to train an additional 300 000 GPs by 2020. This paper examines the perspective of practitioners in Henan, China, regarding general practice. DESIGN: A mixed-methods approach using focus group discussions (FGD), and structured questionnaires. SETTING/PARTICIPANTS: Seven FGDs and responses to 1887 questionnaires included medical students, primary care doctors and GP residents in Henan. RESULTS: The three surveyed medical groups have some awareness of the attributes of general practice (eg, comprehensiveness, first contact and coordination), but often misinterpret what being a GP entails. Five themes were identified through the FGDs and tested quantitatively for their prevalence with structured questionnaires. First, the GPs’ role as a comprehensive care provider was (mis)interpreted as an ‘all-round doctor’. Second, the GP’s responsibility as the first point of care was understood in two conflicting ways: private personal doctors of the rich and the powerful or village doctors for common people. Third, referral was understood as simply guiding patients to appropriate departments within the hospital while the gatekeeping role was interpreted to involve GPs being peoples’ health protectors rather than being also gatekeepers of specialty services. Traditional Chinese medicine now further complicates the understanding of GPs. And lastly, the GPs’ main responsibility was considered to be public health work. CONCLUSION: The misunderstandings of the roles and responsibilities of GPs render problematic the policy foundation of China’s GP-centred primary care system. Pursuing the quantity of GPs on its own is meaningless, since the number needed depends on the delineated role of GPs. Top priority is to establish clarity about the GP role, which requires reforming the health delivery system to address issues with fragmented care, strategically taking into account the development of GPs with work delegation and substitution and providing more clarity on the distinction between general practice and public health.


title: Mild COVID-19 infection despite chronic B cell depletion in a patient with aquaporin-4-positive neuromyelitis Optica spectrum disorder.

text: Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2, which affects the lung and other organs. After an incubation period of 3-14 days, the infection presents with symptoms of variable severity, from mild flu-like disease to severe pneumonia and cytokine storm with increased mortality. Immunosuppressed patients may have higher risk of adverse outcomes; hence, there is an urgent need to evaluate the immune response and clinical outcomes of SARS-CoV-2 infection in these patients. Here, we report a 59-year-old woman with aquaporin-4-positive (AQPR4+) neuromyelitis Optica treated with rituximab who developed mild respiratory symptoms with COVID-19, despite B cell depletion at the time of infection.


Has Hajj-associated Middle East Respiratory Syndrome Coronavirus transmission occurred? The case for effective post-Hajj surveillance for infection


title: The natural history and transmission potential of asymptomatic SARS-CoV-2 infection

text: BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10(th) and April 4(th), 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.


title: Cryptic binding sites on proteins: definition, detection, and druggability

text: Many proteins in their unbound structures lack surface pockets appropriately sized for drug binding. Hence, a variety of experimental and computational tools have been developed for the identification of cryptic sites that are not evident in the unbound protein but form upon ligand binding, and can provide tractable drug target sites. The goal of this review is to discuss the definition, detection, and druggability of such sites, and their potential value for drug discovery. Novel methods based on molecular dynamics simulations are particularly promising and yield a large number of transient pockets, but it has been shown that only a minority of such sites are generally capable of binding ligands with substantial affinity. Based on recent studies, current methodology can be improved by combining molecular dynamics with fragment docking and machine learning approaches.


title: CT Quantitative Analysis and Its Relationship with Clinical Features for Assessing the Severity of Patients with COVID-19

text: OBJECTIVE: To investigate the value of initial CT quantitative analysis of ground-glass opacity (GGO), consolidation, and total lesion volume and its relationship with clinical features for assessing the severity of coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: A total of 84 patients with COVID-19 were retrospectively reviewed from January 23, 2020 to February 19, 2020. Patients were divided into two groups: severe group (n = 23) and non-severe group (n = 61). Clinical symptoms, laboratory data, and CT findings on admission were analyzed. CT quantitative parameters, including GGO, consolidation, total lesion score, percentage GGO, and percentage consolidation (both relative to total lesion volume) were calculated. Relationships between the CT findings and laboratory data were estimated. Finally, a discrimination model was established to assess the severity of COVID-19. RESULTS: Patients in the severe group had higher baseline neutrophil percentage, increased high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and lower baseline lymphocyte count and lymphocyte percentage (p < 0.001). The severe group also had higher GGO score (p < 0.001), consolidation score (p < 0.001), total lesion score (p < 0.001), and percentage consolidation (p = 0.002), but had a lower percentage GGO (p = 0.008). These CT quantitative parameters were significantly correlated with laboratory inflammatory marker levels, including neutrophil percentage, lymphocyte count, lymphocyte percentage, hs-CRP level, and procalcitonin level (p < 0.05). The total lesion score demonstrated the best performance when the data cut-off was 8.2%. Furthermore, the area under the curve, sensitivity, and specificity were 93.8% (confidence interval [CI]: 86.8–100%), 91.3% (CI: 69.6–100%), and 91.8% (CI: 23.0–98.4%), respectively. CONCLUSION: CT quantitative parameters showed strong correlations with laboratory inflammatory markers, suggesting that CT quantitative analysis might be an effective and important method for assessing the severity of COVID-19, and may provide additional guidance for planning clinical treatment strategies.


title: Mass quarantine measures in the time of COVID‐19 pandemic: psychosocial implications for chronic skin conditions and a call for qualitative studies

text: During the ongoing COVID-19 pandemic almost all European countries are adopting mass quarantine or isolation measures as a public health strategy to limit the spread of the contagion. Italy, as the first European country to be deeply affected by such pandemic, is currently approaching the fourth week of total lockdown, with restrictive measures on the population and profound challenge for the national health-care system.


title: Emotional health concerns of oncology physicians in the United States: fallout during the COVID-19 pandemic

text: Introduction: Cancer care is significantly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic. Our objective was to evaluate the effect of the pandemic on the emotional well-being of oncology providers across the United States and explore factors associated with anxiety and depression symptoms. Methods and Materials: A cross-sectional survey was administered to United States cancer-care physicians recruited over a two-week period (3/27/2020-4/10/2020) using snowball-convenience sampling through social media. Symptoms of anxiety and depression were measured using the Patient Health Questionnaire (PHQ-4). Results: Of 486 participants, 374 (77.0%) completed the PHQ-4: mean age 45.7 +/- 9.6 years; 63.2% female; all oncologic specialties were represented. The rates of anxiety and depression symptoms were 62.0% and 23.5%, respectively. Demographic factors associated with anxiety included female sex, younger age, and less time in clinical practice. Perception of inadequate PPE (68.6% vs. 57.4%, p=0.03) and practicing in a state with more COVID-19 cases (65.8% vs. 51.1%, p=0.01) were associated with anxiety symptoms. Factors significantly associated with both anxiety and depression included: degree to which COVID-19 has interfered with the ability to provide treatment to cancer patients and concern that patients will not receive the level of care needed for non-COVID-19 illness (all p-values <0.01). Conclusion: The prevalence of anxiety and depression symptoms among oncology physicians in the United States during the COVID-19 pandemic is high. Our findings highlight factors associated with and sources of psychological distress to be addressed to protect the well-being of oncology physicians.


title: Exploring the Determinants of Perceived Risk of Middle East Respiratory Syndrome (MERS) in Korea

text: The world is turning into a risky society. Although modernization based on the developments in science and technology has increased individuals’ well-being and wealth, the perceived risk toward the complex technological system has increased. In a risky society, social accidents amplify the existing fear among individuals. It is generally assumed that each value, perception, and resource influences the fear of risk. However, very few studies have tested these three factors together within an integrated causal model. Therefore, the present study aimed to examine the determinants that influence the perceived risk in cases of Middle East Respiratory Syndrome (MERS), a deadly epidemic disease, in Korea. Based on the theoretical model, we analyzed the survey data collected from respondents (N = 814) in Korea. After controlling for variables such as sociodemographic characteristics, we examined how three competing factors, i.e., value, perception, and resource, influence the perceived risk of MERS. The analysis showed that trust and vulnerability variables in the perception factor, health state, and perceived knowledge in the resource factor had a significant impact on the perceived risk of MERS.


title: Myocarditis and idiopathic dilated cardiomyopathy

text: Abstract Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.


title: United but divided: policy responses and people's perceptions in the EU during the COVID-19 outbreak

text: To understand the public sentiment toward the measures used by policymakers for COVID-19 containment, a survey among representative samples of the population in seven European countries was carried out in the first two weeks of April 2020. The study addressed people's support for containment policies, worries about COVID-19 consequences, and trust in sources of information. Citizens were overall satisfied with their government's response to the pandemic; however, the extent of approval differed across countries and policy measures. A north-south divide in public opinion was noticeable across the European states. It was particularly pronounced for intrusive policy measures, such as mobile data use for movement tracking, economic concerns, and trust in the information from the national government. Considerable differences in people's attitudes were noticed within countries, especially across individual regions and age groups. The findings suggest that the epidemic acts as a stressor, causing health and economic anxieties even in households that were not directly affected by the virus. At the same time, the burden of stress was unequally distributed across regions and age groups. Based on the data collected, we draw lessons from the containment stage and identify several insights that can facilitate the design of lockdown exit strategies and future containment policies so that a high level of compliance can be expected.


title: Primary Prevention Statins in Older Patients: The Good News or the Bad News First?

text: [Figure: see text]


title: Screening and Identification of Virus-Encoded RNA Silencing Suppressors

text: RNA silencing, including RNA interference, is a novel method of gene regulation and one of the potent host-defense mechanisms against the viruses. In the course of evolution, the viruses have encoded proteins with the potential to suppress the host RNA silencing mechanism as a counterdefense strategy. The virus-encoded RNA silencing suppressors (RSSs) can serve as important biological tools to dissect the detailed RNA silencing pathways and also to evolve the antiviral strategies. Screening and identification of the RSSs are indeed of utmost significance in the field of plant biotechnology. We describe two Green Fluorescent Protein (GFP) reporter-based plant assay systems that rely on two different principles, namely reversal of silencing and enhancement of rolling circle replication (RCR) of geminiviral replicon. These proof-of-concept examples and assay systems could be used to screen various plant, animal, and insect viral ORFs for identification of the RSS activities.


title: Testing pollution haven and pollution halo hypotheses for Turkey: a new perspective

text: In this study, we analyzed the asymmetric short- and long-run causal links between foreign direct investments and emissions in Turkey over the time period 1974–2018. Using hidden co-integration techniques, we defined and tested the asymmetric pollution haven and asymmetric pollution halo hypotheses. To evaluate the long-run asymmetric causal relationship, we estimated both the crouching error correction model and vector error correction model. We performed a stepwise regression model to estimate the crouching error correction model. The empirical results confirmed an asymmetric causal relationship between positive shocks of foreign direct investments and positive movements in emissions in the short run as well as an asymmetric causal link between negative and positive shocks of foreign direct investments and positive emissions in the long run. Furthermore, the results showed that increases in foreign direct investments led to a decrease in the rate of emission growth in both the short and long run. This finding supports the validity of the asymmetric pollution halo hypothesis in Turkey’s case. Policymakers should strengthen their environmental protection laws to protect the quality of their environments as well as implement policies that encourage the use of clean technology and tax incentives that increase foreign direct investment inflows. [Figure: see text]


title: Hepatitis C virus vaccine design: focus on the humoral immune response

text: Despite the recent development of safe and highly effective direct-acting antivirals, hepatitis C virus (HCV) infection remains a significant health problem. In 2016, the World Health Organization set out to reduce the rate of new HCV infections by 90% by 2030. Still, global control of the virus does not seem to be achievable in the absence of an effective vaccine. Current approaches to the development of a vaccine against HCV include the production of recombinant proteins, synthetic peptides, DNA vaccines, virus-like particles, and viral vectors expressing various antigens. In this review, we focus on the development of vaccines targeting the humoral immune response against HCV based on the cumulative evidence supporting the important role of neutralizing antibodies in protection against HCV infection. The main targets of HCV-specific neutralizing antibodies are the glycoproteins E1 and E2. Recent advances in the knowledge of HCV glycoprotein structure and their epitopes, as well as the possibility of getting detailed information on the human antibody repertoire generated by the infection, will allow rational structure-based antigen design to target specific germline antibodies. Although obtaining a vaccine capable of inducing sterilizing immunity will be a difficult task, a vaccine that prevents chronic hepatitis C infections, a more realistic goal in the short term, would have a considerable health impact.


title: A Retrospective Cohort Study of an Outbreak of Cryptosporidiosis among Veterinary Students

text: An outbreak of gastrointestinal illness occurred among a cohort of 56 veterinary technology and 100 veterinary science students at Massey University over an eight-week period in 2013. This coincided with calving in New Zealand’s seasonal dairy farming system and a time when calves with diarrhoea are commonly seen by veterinarians. Laboratory and epidemiological investigations were instigated by MidCentral Public Health Service (MCPHS) in conjunction with the Institute of Veterinary, Animal and Biomedical Sciences (IVABS) at Massey University. Eighty students responded to a questionnaire of which 19 met the case definition, a 24% attack rate. Faecal specimens from seven students contained Cryptosporidium oocysts and Cryptosporidium parvum IIa A18G3R1 was identified from one of the specimens. The inferred median incubation period was five days (range 1–12 days). All of the cases were self-limiting, characterized by diarrhoea, abdominal cramps, and in some cases vomiting, headache, and fever. Having contact with calves with diarrhoea was significantly associated with increased adjusted odds of being a case (OR 10.61, 95% CI 1.87–108.29 for one week of contact; OR 55.05, 95% CI 3.80–1931.18 for two weeks of contact). Outbreaks of cryptosporidiosis had occurred previously among veterinary students at Massey University, but the extremely high infectivity of C. parvum resulted in student illness despite enhanced hygiene precautions.


title: Meeting report: 29th International Conference on Antiviral Research in La Jolla, CA, USA

text: Abstract The 29th International Conference on Antiviral Research (ICAR) was held in La Jolla, CA, USA from April 17 to 21, 2016. This report opens with a tribute to the late Chris McGuigan, a Past-President of ISAR, then continues with summaries of the principal invited lectures. Doug Richman (Elion Award) investigated HIV resistance, Bob Vince (Holý Award) showed how carbocyclic nucleoside analogs led to abacavir and Jerome Deval (Prusoff Award) explained how his group chose to seek a nucleoside analog to treat RSV. ALS-8176 was active in a human RSV-challenge study and is being evaluated in children. The first keynote address, by Richard H. Scheuermann, reported on the remarkable progress made in viral genomics. The second keynote address, by Heinz Feldmann, gave an overview of Ebola virus disease. There were four mini-symposia, Structural Biology, Diagnostic Technologies, DNA viruses and Zika virus. Diagnostic assays are approaching an ideal aim, a compact instrument, simple to use with any type of sample, no sample preparation and a result within an hour. The diversity of HCMV is far greater than for other herpesviruses, typically, an individual having >20,000 single nucleotide polymorphisms (SNPs). During antiviral treatment, there is rapid CMV evolution which is presumed to be due to preferential selection of already present variants rather than by the creation of new variants. A selection of contributor presentations includes oral prodrugs for nucleoside triphosphate analogs, a new method for the synthesis of phosphoramidate prodrugs and the clinical evaluation of brincidofovir for treating transplant recipients with adenovirus infections.


COVID‐19 and human–virus relationality


Crouching Tiger, Hidden Dragon: The Laboratory Diagnosis of Severe Acute Respiratory Syndrome


title: Diversity of Middle East respiratory syndrome coronaviruses in 109 dromedary camels based on full-genome sequencing, Abu Dhabi, United Arab Emirates

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was identified on the Arabian Peninsula in 2012 and is still causing cases and outbreaks in the Middle East. When MERS-CoV was first identified, the closest related virus was in bats; however, it has since been recognized that dromedary camels serve as a virus reservoir and potential source for human infections. A total of 376 camels were screened for MERS-Cov at a live animal market in the Eastern Region of the Emirate of Abu Dhabi, UAE. In all, 109 MERS-CoV-positive camels were detected in week 1, and a subset of positive camels were sampled again weeks 3 through 6. A total of 126 full and 3 nearly full genomes were obtained from 139 samples. Spike gene sequences were obtained from 5 of the 10 remaining samples. The camel MERS-CoV genomes from this study represent 3 known and 2 potentially new lineages within clade B. Within lineages, diversity of camel and human MERS-CoV sequences are intermixed. We identified sequences from market camels nearly identical to the previously reported 2015 German case who visited the market during his incubation period. We described 10 recombination events in the camel samples. The most frequent recombination breakpoint was the junctions between ORF1b and S. Evidence suggests MERS-CoV infection in humans results from continued introductions of distinct MERS-CoV lineages from camels. This hypothesis is supported by the camel MERS-CoV genomes sequenced in this study. Our study expands the known repertoire of camel MERS-CoVs circulating on the Arabian Peninsula.


title: The Origin and Evolution of Variable Number Tandem Repeat of CLEC4M Gene in the Global Human Population

text: CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes) from the (Human Genome Diversity Panel) HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats) were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate) mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.


Reply to: Letter to the Editor: Screening All Pregnant Women Admitted to Labor and Delivery for the Virus Responsible for COVID-19


title: Incidental COVID-19 related lung apical findings on stroke CTA during the COVID-19 pandemic

text: BACKGROUND: Authors have noticed an increase in lung apex abnormalities on CT angiography (CTA) of the head and neck performed for stroke workup during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To evaluate the incidence of these CTA findings and their relation to COVID-19 infection. METHODS: In this retrospective multicenter institutional review board-approved study, assessment was made of CTA findings of code patients who had a stroke between March 16 and April 5, 2020 at six hospitals across New York City. Demographic data, comorbidities, COVID-19 status, and neurological findings were collected. Assessment of COVID-19 related lung findings on CTA was made blinded to COVID-19 status. Incidence rates of COVID-19 related apical findings were assessed in all code patients who had a stroke and in patients with a stroke confirmed by imaging. RESULTS: The cohort consisted of a total of 118 patients with mean±SD age of 64.9±15.7 years and 57.6% (68/118) were male. Among all code patients who had a stroke, 28% (33/118) had COVID-19 related lung findings. RT-PCR was positive for COVID-19 in 93.9% (31/33) of these patients with apical CTA findings. Among patients who had a stroke confirmed by imaging, 37.5% (18/48) had COVID-19 related apical findings. RT-PCR was positive for COVID-19 in all (18/18) of these patients with apical findings. CONCLUSION: The incidence of COVID-19 related lung findings in stroke CTA scans was 28% in all code patients who had a stroke and 37.5% in patients with a stroke confirmed by imaging. Stroke teams should closely assess the lung apices during this COVID-19 pandemic as CTA findings may be the first indicator of COVID-19 infection.


title: Personal health of spine surgeons can impact perceptions, decision-making and healthcare delivery during the COVID-19 pandemic-a worldwide study

text: Objective: To determine if personal health of spine surgeons worldwide influences percep-tions, healthcare delivery, and decision-making during the coronavirus disease 2019 (CO-VID-19) pandemic. Methods: A cross-sectional study was performed by distributing a multidimensional survey to spine surgeons worldwide. Questions addressed demographics, impacts and perceptions of COVID-19, and the presence of surgeon comorbidities, which included cancer, cardiac disease, diabetes, obesity, hypertension, respiratory illness, renal disease, and current tobacco use. Multivariate analysis was performed to identify specific comorbidities that influenced various impact measures. Results: Across 7 global regions, 36.8% out of 902 respondents reported a comorbidity, of which hypertension (21.9%) and obesity (15.6%) were the most common. Multivariate analysis noted tobacco users were more likely to continue performing elective surgery during the pandemic (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.46–4.72; p = 0.001) and were less likely to utilize telecommunication (OR, 0.51; 95% CI, 0.31–0.86; p = 0.011), whereas those with hypertension were less likely to warn their patients should the surgeon become infected with COVID-19 (OR, 0.57; 95% CI, 0.37–0.91; p = 0.017). Clinicians with multiple comorbidities were more likely to cite personal health as a current stressor (OR, 1.32; 95% CI, 1.07–1.63; p = 0.009) and perceived their hospital’s management un-favorably (OR, 0.74; 95% CI, 0.60–0.91; p = 0.005). Conclusion: This is the first study to have mapped global variations of personal health of spine surgeons, key in the development for future wellness and patient management initia-tives. This study underscored that spine surgeons worldwide are not immune to comorbidi-ties, and their personal health influences various perceptions, healthcare delivery, and de-cision-making during the COVID-19 pandemic.


title: No-Notice Mystery Patient Drills to Assess Emergency Preparedness for Infectious Diseases at Community Health Centers in New York City, 2015–2016

text: Mystery patient drills using simulated patients have been used in hospitals to assess emergency preparedness for infectious diseases, but these drills have seldom been reported in primary care settings. We conducted three rounds of mystery patient drills designed to simulate either influenza-like illness (ILI) or measles at 41 community health centers in New York City from April 2015 through December 2016. Among 50 drills conducted, 49 successfully screened the patient–actor (defined as provision of a mask or referral to the medical team given concern of infection requiring potential isolation), with 35 (70%) drills completing screening without any challenges. In 47 drills, the patient was subsequently isolated (defined as placement in a closed room to limit transmission), with 29 (58%) drills completing isolation without any challenges. Patient–actors simulating ILI were more likely to be masked than those simulating measles (93% vs. 59%, p = 0.007). Median time to screening was 2 min (interquartile range [IQR] 2–6 min) and subsequently to isolation was 1 min (IQR 0–2 min). Approximately 95% of participants reported the drill was realistic and prepared them to deal with the hazards addressed. Qualitative analysis revealed recurring themes for strengths (e.g., established protocols, effective communication) and areas for improvement (e.g., hand hygiene, explaining isolation rationale). We conclude that mystery patient drills are an effective and feasible longitudinal collaboration between health departments and primary care clinics to assess and inform emergency preparedness for infectious diseases.


Rapid COVID-19–related Clinical Adaptations and Unanticipated Risks


title: Inter-generational Effects of Technology: Why Millennial Physicians May Be Less at Risk for Burnout Than Baby Boomers

text: PURPOSE OF REVIEW: Younger generations of physicians are using technology more fluently than previous generations. This has significant implications for healthcare as these digital natives become a majority of the population’s patients, clinicians, and healthcare leaders. RECENT FINDINGS: Historically, healthcare has been slow to adopt new technology. Many physicians have attributed burnout symptoms to technology-related causes like the EMR. This is partly due to policies and practices led by those who were less familiar and comfortable with using new technologies. SUMMARY: Younger physicians will drive technological advancement and integration faster than previous generations, allowing technology to adapt more quickly to serve the needs of clinicians and patients. These changes will improve efficiency, allow more flexible working arrangements, and increase convenience for patients and physicians. The next generation of physicians will use technology to support their work and lifestyle preferences, making them more resilient to burnout than previous generations.


title: Non-Sexually transmitted infectious diseases of the oral, nasal, and vaginal mucosae

text: Abstract The skin and mucous membranes are the principal barriers to invasion of the body by microorganisms. Besides functioning as a mechanical barrier, the mucosae are endowed with an array of still poorly characterized specific and nonspecific host defense capabilities. These include the production of mucus, secretory immunoglobulin (IgA), lysozyme, lactoferrin, and alpha-antitrypsin, in conjunction with a low-grade exudation of leukocytes.1 In addition, the mucosal surfaces of the upper respiratory, gastrointestinal, and lower vaginal and urinary tracts support a large number of “nonpathogenic” microorganisms that comprise the so-called “normal flora.” This commensal flora plays an important and complex role in protecting the host from microbial invasion. Mechanisms for this protection likely include the following: (1) competition for the same nutrients (interference); (2) competition for the same receptors on host cells (tropism); (3) production of bacteriocins, that is, bacterial products that are toxic to other organisms, usually of the same species; and (4) stimulation of crossprotective immune factors such as the “natural antibodies.”1 The “normal” flora is inconstant and may be altered by dietary factors, debilitation, hormonal events (such as menstruation, pregnancy, and possibly use of oral contraceptives), personal hygiene, medications, intercurrent infection, and probably many others. Antibiotic therapy and menstruation can have a profound effect on the composition of this group of microorganisms.2 Disturbance of the delicate host-commensal relationship may cause a clinically significant infection due to these “nonpathogens.” This may occur in response to the aforementioned factors (eg, pregnancy predisposing to vaginal candidiasis) or because of disruption of the anatomic barrier (eg, local mucosal infection at a site of trauma, or injury from cytotoxic drugs) or in association with exogenous infection (eg, rhinoviral infection leading to secondary bacterial otitis media). Invasion by “normal flora” may result in serious systemic illness. A clear example of the latter is the development of infective endocarditis caused by viridans streptococci following a dental procedure.


title: A Real-Time Autonomous Dashboard for the Emergency Department: 5-Year Case Study

text: BACKGROUND: The task of monitoring and managing the entire emergency department (ED) is becoming more important due to increasing pressure on the ED. Recently, dashboards have received the spotlight as health information technology to support these tasks. OBJECTIVE: This study aimed to describe the development of a real-time autonomous dashboard for the ED and to evaluate perspectives of clinical staff on its usability. METHODS: We developed a dashboard based on three principles—“anytime, anywhere, at a glance;” “minimal interruption to workflow;” and “protect patient privacy”—and 3 design features—“geographical layout,” “patient-level alert,” and “real-time summary data.” Items to evaluate the dashboard were selected based on the throughput factor of the conceptual model of ED crowding. Moreover, ED physicians and nurses were surveyed using the system usability scale (SUS) and situation awareness index as well as a questionnaire we created on the basis of the construct of the Situation Awareness Rating Technique. RESULTS: The first version of the ED dashboard was successfully launched in 2013, and it has undergone 3 major revisions since then because of geographical changes in ED and modifications to improve usability. A total of 52 ED staff members participated in the survey. The average SUS score of the dashboard was 67.6 points, which indicates “OK-to-Good” usability. The participants also reported that the dashboard provided efficient “concentration support” (4.15 points), “complexity representation” (4.02 points), “variability representation” (3.96 points), “information quality” (3.94 points), and “familiarity” (3.94 points). However, the “division of attention” was rated at 2.25 points. CONCLUSIONS: We developed a real-time autonomous ED dashboard and successfully used it for 5 years with good evaluation from users.


title: Broad-spectrum antiviral and cytocidal activity of cyclopentenylcytosine, a carbocyclic nucleoside targeted at CTP synthetase

text: Abstract Cyclopentenylcytosine (Ce-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [herpes (cytomegalo), pox (vaccinia)], (+)RNA viruses [picorna (polio, Coxsackie, rhino), toga (Sindbis, Semliki forest), corona], (−)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), arena (Junin, Tacaribe), rhabdo (vesicular stomatitis)] and (±)RNA viruses (reo). Ce-Cyd is a more potent antiviral agent than its saturated counterpart, cyclopentylcytosine (carbodine, C-Cyd). Ce-Cyd also has potent cytocidal activity against a number of tumor cell lines. The putative target enzyme for both the antiviral and antitumor action of Ce-Cyd is assumed to be the CTP synthetase that converts UTP to CTP. In keeping with this hypothesis was the finding that the antiviral and cytocidal effects of Ce-Cyd are readily reversed by Cyd and, to a lesser extent, Urd, but not by other nucleosides such as dThd or dCyd. In contrast, pyrazofurin and 6-azauridine, two nucleoside analogues that are assumed to interfere with OMP decarboxylase, another enzyme involved in the biosynthesis of pyrimidine ribonucleotides, potentiate the cytocidal activity of Ce-Cyd. Ce-Cyd should be further pursued, as such and in combination with OMP decarboxylase inhibitors, for its therapeutic potential in the treatment of both viral and neoplastic diseases.


title: First COVID-19 sub-intensive respiratory unit in Europe: the Italian experience

text: European SARS-CoV-2 pandemic epicenter was detected in Northern Italy, in a little Italian town of Lodi province, the Lodi Hospital was therefore rapidly saturated, and in particularly the departments of respiratory diseases and Intensive Care Unit had been largely involved. In this paper, we describe how the first Sub-intensive Respiratory Unit in Europe completely dedicated to COVID-19 patients was organized and managed in our hospital. From February 25(th) to April 30(th) 2020, 156 patients were admitted to our Respiratory Sub-intensive Unit. Among them, 100 were discharged, 28 dead and 28 transferred to ICU for intubation.


Section 4: Immunopharmacology


Incidence of invasive pulmonary aspergillosis among critically ill COVID-19 patients


title: Dengue fever in travellers: A challenge for European physicians

text: Abstract Dengue fever (DF) is one of the world's emerging infectious diseases. The steady increase in European tourists, as well as soldiers serving on peacekeeping duties, in endemic areas, coupled with the present resurgence of dengue, raises the risk of exposure for a large number of European travellers. Significant numbers of travellers have, in fact, developed DF. There is a risk of dengue haemorrhagic fever (DHF) in travellers who revisit the same place, and they have the potential not only to acquire, but also to spread, the dengue viral infection. Of concern is the potential for a dengue outbreak in a previously dengue-free country through imported cases. Another major concern is the potential area of dengue transmission, due to spread of its vectors through sizeable parts of southern Europe. In addition to the risk of haemorrhagic fever in returning tourists, the introduction of DF by returning travellers, whether they have symptoms or are unaffected by signs and symptoms of the disease, poses a threat to health systems in Europe.


title: Diagnosis of Parasitic Diseases: Old and New Approaches

text: Methods for the diagnosis of infectious diseases have stagnated in the last 20–30 years. Few major advances in clinical diagnostic testing have been made since the introduction of PCR, although new technologies are being investigated. Many tests that form the backbone of the “modern” microbiology laboratory are based on very old and labour-intensive technologies such as microscopy for malaria. Pressing needs include more rapid tests without sacrificing sensitivity, value-added tests, and point-of-care tests for both high- and low-resource settings. In recent years, research has been focused on alternative methods to improve the diagnosis of parasitic diseases. These include immunoassays, molecular-based approaches, and proteomics using mass spectrometry platforms technology. This review summarizes the progress in new approaches in parasite diagnosis and discusses some of the merits and disadvantages of these tests.


title: Chapter 7 Carbohydrate Microarrays for Lectin Characterization and Glyco-Epitope Identification

text: Publisher Summary Lectins can also be classified according to their binding specificity or selectivity with carbohydrates. This type of classification is helpful for selection of lectins as structural probes in biomedical applications. This chapter summarizes the concept and the updated information regarding the specificity-based lectin classification. Lectins are functionally classified based on their relative binding reactivities with the structural units of carbohydrate or glyco-epitopes. They are grouped according to their monosaccharide specificities and then further sub-grouped based on their reactivities with more complex structures. Carbohydrate specificities of biomedically important lectins are classified into six groups according to their specificities to monosaccharides. The chapter introduces a practical platform of carbohydrate microarrays that is useful for lectin characterization and classification. Finally, the chapter discusses a few examples to illustrate the application of this technology in lectin-related experimental investigations.


title: Analysis and visualization of H7 influenza using genomic, evolutionary and geographic information in a modular web service

text: We have reported previously on use of a web‐based application, Supramap (http://supramap.org) for the study of biogeographic, genotypic, and phenotypic evolution. Using Supramap we have developed maps of the spread of drug‐resistant influenza and host shifts in H1N1 and H5N1 influenza and coronaviruses such as SARS. Here we report on another zoonotic pathogen, H7 influenza, and provide an update on the implementation of Supramap as a web service. We find that the emergence of pathogenic strains of H7 is labile with many transitions from high to low pathogenicity, and from low to high pathogenicity. We use Supramap to put these events in a temporal and geospatial context. We identify several lineages of H7 influenza with biomarkers of high pathogenicity in regions that have not been reported in the scientific literature. The original implementation of Supramap was built with tightly coupled client and server software. Now we have decoupled the components to provide a modular web service for POY (http://poyws.org) that can be consumed by a data provider to create a novel application. To demonstrate the web service, we have produced an application, Geogenes (http://geogenes.org). Unlike in Supramap, in which the user is required to create and upload data files, in Geogenes the user works from a graphical interface to query an underlying dataset. Geogenes demonstrates how the web service can provide underlying processing for any sequence and metadata database. © The Willi Hennig Society 2012.


title: Coronaviruses in cats and other companion animals: Where does SARS-CoV-2/COVID-19 fit?

text: • Coronaviruses are wide-ranging diseases in humans and animals. • SARS-CoV-2 is a bat-origin zoonotic coronavirus causing the COViD-19 pandemic. • SARS-CoV-2 can also infect cats and ferrets and has been detected in dogs. • The SARS-CoV-2 receptor ACE2 is highly similar between cats and humans.


title: Spectrum of respiratory viruses circulating in eastern India: Prospective surveillance among patients with influenza‐like illness during 2010–2011

text: In developing countries, viruses causing respiratory disease are a major concern of public health. During January 2010–December 2011, 2,737 patients with acute respiratory infection from the outpatient departments as well as patients admitted to hospitals were screened for different respiratory viruses. Nasal and or throat swabs were collected and transported to the laboratory where initial screening of influenza A and influenza B viruses was performed. The samples were tested further for influenza C virus, parainfluenza viruses 1–4, human rhinovirus, metapneumovirus and respiratory syncytial virus by conventional RT‐ PCR. The study revealed that the majority of the patients were under 5 years of age; both due to their higher susceptibility to respiratory infections and presentation to hospitals. Out of 2,737 patients enrolled in this study, 59% were found positive for one or more respiratory viruses. Influenza B infection was detected in 12% of patients followed by influenza A (11.7%), respiratory syncytial virus (7.1%), parainfluenza virus‐2 (6%), metapneumovirus (3%), parainfluenza virus‐3 (1%), parainfluenza virus‐4 (0.6%), parainfluenza virus‐1 (0.3%), influenza C (0.2%) and human rhinovirus (0.2%). Distinct seasonal infection was observed only for influenza A and influenza B viruses. J. Med. Virol. 85:1459–1465, 2013. © 2013 Wiley Periodicals, Inc.


No chisels


title: Entry of Newcastle Disease Virus into the host cell: Role of acidic pH and endocytosis

text: Abstract Most paramyxoviruses enter the cell by direct fusion of the viral envelope with the plasma membrane. Our previous studies have shown the colocalization of Newcastle Disease Virus (NDV) with the early endosome marker EEA1 and the inhibition of NDV fusion by the caveolin-phosphorylating drug phorbol 12-myristate 13-acetate (PMA) prompted us to propose that NDV enters the cells via endocytosis. Here we show that the virus-cell fusion and cell-cell fusion promoted by NDV-F are increased by about 30% after brief exposure to low pH in HeLa and ELL-0 cells but not in NDV receptor- deficient cell lines such as GM95 or Lec1. After a brief low-pH exposure, the percentage of NDV fusion at 29 °C was similar to that at 37 °C without acid-pH stimulation, meaning that acid pH would decrease the energetic barrier to enhance fusion. Furthermore, preincubation of cells with the protein kinase C inhibitor bisindolylmaleimide led to the inhibition of about 30% of NDV infectivity, suggesting that a population of virus enters cells through receptor-mediated endocytosis. Moreover, the involvement of the GTPase dynamin in NDV entry is shown as its specific inhibitor, dynasore, also impaired NDV fusion and infectivity. Optimal infection of the host cells was significantly affected by drugs that inhibit endosomal acidification such as concanamycin A, monensin and chloroquine. These results support our hypothesis that entry of NDV into ELL-0 and HeLa cells occurs through the plasma membrane as well as by dynamin- low pH- and receptor- dependent endocytosis.


title: Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial

text: BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.


title: A Rare Cause of Childhood Cerebellitis-Influenza Infection: A Case Report and Systematic Review of Literature

text: Acute cerebellitis is a benign neurologic condition generally caused by viral or bacterial infections. Influenza associated cerebellitis is extremely rare; a 6-year-old boy with acute cerebellitis, who presented with fever, vomiting, weakness, febrile seizure, and acute cerebellar features, is discussed in this article.


title: Soluble cytoplasmic expression, rapid purification, and characterization of cyanovirin-N as a His-SUMO fusion

text: Cyanovirin-N (CVN) is a promising antiviral candidate that has an extremely low sequence homology with any other known proteins. The efficient and soluble expression of biologically functional recombinant CVN (rCVN) is still an obstacle due to insufficient yield, aggregation, and abnormal modification. Here, we describe an improved approach to preparing native rCVN from Escherichia coli more efficiently. A fusion gene consisting of cvn and sumo (small ubiquitin-related modifier) and a hexahistidine tag was constructed according to the codon bias of the host cell. This small ubiquitin-related modifier (SUMO)-fused CVN is expressed in the cytoplasm of E. coli in a folded and soluble form (>30% of the total soluble protein), yielding 3 to 4 mg of native rCVN from 1 g of wet cells to a purity up to 97.6%. Matrix-assisted laser desorption ionization coupled to time-of-flight mass spectrometry and reverse-phase high-performance liquid chromatographic analysis showed that the purified rCVN was an intact and homogeneous protein with a molecular weight of 11,016.68 Da. Potent antiviral activity of rCVN against herpes simplex virus type 1 and human immunodeficiency virus type 1/IIIB was confirmed in a dose-dependent manner at nanomolar concentrations. Thus, the His-SUMO double-fused CVN provides an efficient approach for the soluble expression of rCVN in the cytoplasm of E. coli, allowing an alternative system to develop bioprocess for the large-scale production of this antiviral candidate.


title: Assessment of Health Information About COVID-19 Prevention on the Internet: Infodemiological Study

text: BACKGROUND: The internet is a large source of health information and has the capacity to influence its users. However, the information found on the internet often lacks scientific rigor, as anyone may upload content. This factor is a cause of great concern to scientific societies, governments, and users. OBJECTIVE: The objective of our study was to investigate the information about the prevention of coronavirus disease 2019 (COVID-19) on the internet. METHODS: On February 29, 2020, we performed a Google search with the terms “Prevention coronavirus,” “Prevention COVID-19,” “Prevención coronavirus,” and “Prevención COVID-19”. A univariate analysis was performed to study the association between the type of authorship, country of publication, and recommendations to avoid COVID-19 according to the World Health Organization (WHO). RESULTS: In total, 80 weblinks were reviewed. Most of them were produced in the United States and Spain (n=58, 73%) by digital media sources and official public health organizations (n=60, 75%). The most mentioned WHO preventive measure was “wash your hands frequently” (n=65, 81%). A less frequent recommendation was to “stay home if you feel unwell” (n=26, 33%). The analysis by type of author (official public health organizations versus digital media) revealed significant differences regarding the recommendation to wear a mask when you are healthy only if caring for a person with suspected COVID-19 (odds ratio [OR] 4.39). According to the country of publication (Spain versus the United States), significant differences were detected regarding some recommendations such as “wash your hands frequently” (OR 9.82), “cover your mouth and nose with your bent elbow or tissue when you cough or sneeze” (OR 4.59), or “stay home if you feel unwell” (OR 0.31). CONCLUSIONS: It is necessary to urge and promote the use of the websites of official public health organizations when seeking information on COVID-19 preventive measures on the internet. In this way, users will be able to obtain high-quality information more frequently, and such websites may improve their accessibility and positioning, given that search engines justify the positioning of links obtained in a search based on the frequency of access to them.


title: The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models

text: In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS‐CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS‐CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.


title: Modelling the spread of COVID-19 with new fractal-fractional operators: Can the lockdown save mankind before vaccination?

text: Countries around the world are implementing lock-down measures in a bid to flatten the curve of the new deadly COVID-19 disease. Our paper does not claim to have found the cure for COVID-19, neither does it claim that the suggested model have taken into account all the complexities around the spread of the disease. Nonetheless, the fundamental question asked in this paper is to know if within the conditions taken into account in this suggested model, the integral lock-down is effective in saving human lives. To answer this question, a mathematical model was suggested taking into account the possibility of transmission of COVID-19 from dead bodies to humans and the effect of lock-down. Three cases were considered. The first case suggested that there is transmission from dead to the living (medical staffs as they perform postmortem procedures on corpses, and direct contacts with during burial ceremonies). This case has no equilibrium points except for disease free equilibrium, a clear indication that care must be taken when dealing with corpses due to corona-19. In the second case we removed the transmission rate from dead bodies. This case showed an equilibrium point, although the number of deaths, carriers and infected grew exponentially up to a certain stability level. In the last case, we incorporated a lock-down and social distancing effect, using the next generation matrix. We could achieve a zero reproduction number, with number of deaths, infected and carriers decaying very rapidly. This is a clear indication that if lock-down recommendations are observed the threat of COVID-19 can be reduced to zero in few months.While our mathematical model agrees with the effectiveness of the lock-down, it is important to mention damaging effects of inadequate testing. The long waiting period of few days before confirmation of status, can only lead to more infections. The asymptomatic tested person could be positive and spread the infection, or could contact the virus in days after testing and will spread the disease further, after being given a false result. Testing kit that with immediate results are needed for more efficient measures. We used Italy’s Data to guide the construction of the mathematical model. To include non-locality into mathematical formulas, differential and integral operators were suggested. Properties and numerical approximations were presented in details. Finally, the suggested differential and integral operators were applied to the model.


title: Preparedness of institutions around the world for managing patients with Ebola virus disease: an infection control readiness checklist

text: BACKGROUND: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola Infection Control Readiness Checklist to assess the preparedness of institutions around the globe. We report data from the electronic checklist that was disseminated to medical professionals from October to December 2014 and identify action needed towards better preparedness levels. FINDINGS: Data from 192 medical professionals (one third from Africa) representing 125 hospitals in 45 countries around the globe were obtained through a specifically developed electronic survey. The survey contained 76 specific questions in 7 major sections: Administrative/operational support; Communications; Education and audit; Human resources, Supplies, Infection Prevention and Control practices and Clinical management of patients. The majority of respondents were infectious disease specialists/infection control consultants/clinical microbiologists (75; 39 %), followed by infection control professionals (59; 31 %) and medical doctors of other specialties (17; 9 %). Nearly all (149; 92 %) were directly involved in Ebola preparedness activities. Whilst, 54 % indicated that their hospital would need to handle suspected and proven Ebola cases, the others would subsequently transfer suspected cases to a specialized centre. CONCLUSION: The results from our survey reveal that the general preparedness levels for management of potentially suspected cases of Ebola virus disease is only partially adequate in hospitals. Hospitals designated for admitting EVD suspected and proven patients had more frequently implemented Infection Control preparedness activities than hospitals that would subsequently transfer potential EVD cases to other centres. Results from this first international survey provide a framework for future efforts to improve hospital preparedness worldwide. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13756-015-0061-8) contains supplementary material, which is available to authorized users.


title: The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells

text: The Notch signaling pathway plays important roles in a variety of cellular processes. Aberrant transduction of Notch signaling contributes to many diseases and cancers in humans. The Notch receptor intracellular domain, the activated form of Notch receptor, is extremely difficult to detect in normal cells. However, it can activate signaling at very low protein concentration to elicit its biological effects. In the present study, a cell based luciferase reporter gene assay was established in K562 cells to screen drugs which could modulate the endogenous CBF1‐dependent Notch signal pathway. Using this system, we found that the luciferase activity of CBF1‐dependent reporter gene was activated by baicalin and baicalein but suppressed by niclosamide in both dose‐ and time‐dependent manners. Treatment with these drugs modulated endogenous Notch signaling and affected mRNA expression levels of Notch1 receptor and Notch target genes in K562 cells. Additionally, erythroid differentiation of K562 cells was suppressed by baicalin and baicalein yet was promoted by niclosamide. Colony‐forming ability in soft agar was decreased after treatment with baicalin and baicalein, but was not affected in the presence of niclosamide. Thus, modulation of Notch signaling after treatment with any of these three drugs may affect tumorigenesis of K562 cells suggesting that these drugs may have therapeutic potential for those tumors associated with Notch signaling. Taken together, this system could be beneficial for screening of drugs with potential to treat Notch signal pathway‐associated diseases. J. Cell. Biochem. 106: 682–692, 2009. © 2009 Wiley‐Liss, Inc.


title: Bronchiolite del lattante

text: La bronchiolite è un’infezione virale stagionale delle vie respiratorie basse del lattante. Il suo agente causale principale è il virus respiratorio sinciziale. La comparsa di un distress respiratorio è legata all’intensità della risposta infiammatoria delle vie aeree. Benché si tratti di una malattia frequente, le cause della suscettibilità dei lattanti a questa infezione non sono conosciute. La diagnosi è clinica. Il trattamento è sintomatico in assenza di misure specifiche. I rapporti a medio e a lungo termine di un primo episodio di bronchiolite con le recidive e con l’asma non sono spiegati. Essi potrebbero dipendere dalla natura del virus in causa al momento del primo episodio e da fattori genetici individuali.


title: Comparison of the conventional multiplex RT–PCR, real time RT–PCR and Luminex xTAG(®) RVP fast assay for the detection of respiratory viruses

text: Detection of respiratory viruses using polymerase chain reaction (PCR) is sensitive, specific and cost effective, having huge potential for patient management. In this study, the performance of an in‐house developed conventional multiplex RT–PCR (mRT–PCR), real time RT–PCR (rtRT–PCR) and Luminex xTAG(®) RVP fast assay (Luminex Diagnostics, Toronto, Canada) for the detection of respiratory viruses was compared. A total 310 respiratory clinical specimens predominantly from pediatric patients, referred for diagnosis of influenza A/H1N1pdm09 from August 2009 to March 2011 were tested to determine performance characteristic of the three methods. A total 193 (62.2%) samples were detected positive for one or more viruses by mRT–PCR, 175 (56.4%) samples by real time monoplex RT‐PCR, and 138 (44.5%) samples by xTAG(®) RVP fast assay. The overall sensitivity of mRT–PCR was 96.9% (95% CI: 93.5, 98.8), rtRT–PCR 87.9% (95% CI: 82.5, 92.1) and xTAG(®) RVP fast was 68.3% (95% CI: 61.4, 74.6). Rhinovirus was detected most commonly followed by respiratory syncytial virus group B and influenza A/H1N1pdm09. The monoplex real time RT–PCR and in‐house developed mRT‐PCR are more sensitive, specific and cost effective than the xTAG(®) RVP fast assay. J. Med. Virol. 88:51–57, 2016. © 2015 Wiley Periodicals, Inc.


title: High Frequency of Antiphospholipid Antibodies in Critically‐ill COVID‐19 Patients: a Link with Hypercoagulability?

text: Coronavirus disease 2019 (COVID‐19) is associated with both severe systemic inflammation and a prothrombotic state, as reflected by significant increases in fibrinogen and D‐dimers levels that have been associated with poor prognosis and high rates of severe pulmonary embolism. A recent report suggested a role for antiphospholipid antibodies (aPLA) in the thrombotic manifestations associated with severe COVID‐19. As we also recently noticed unexplained lengthening of activated partial thromboplastin time (aPTT) in some critically ill COVID‐19 patients, we explored our patients for aPLA positivity.


title: Predictors for compliance of standard precautions among nursing students

text: BACKGROUND: We aimed to investigate the frequency of standard precautions (SPs) compliance and the factors affecting the compliance among nursing students (NSs). METHODS: A cross-sectional survey study guided by the health belief model was conducted in 2009. The study questionnaire is valid (content validity index, 0.81) and reliable (Cronbach α range, 0.65-0.94). RESULTS: There were 678 questionnaires analyzed, with a response rate of 68.9%. The mean frequency score of SPs compliance was 4.38 ± 0.40 out of 5. Tukey honest significant difference post hoc test indicated that year 2 and year 4 students had better SPs compliance than year 3 students. Further analysis using a univariate general linear model identified an interaction effect of perceived influence of nursing staff and year of study (F(1,593) = 3.72; P < .05). The 5 following predictors for SPs compliance were identified: knowledge of SPs, perceived barriers, adequacy of training, management support, and influence of nursing staff. CONCLUSION: Although the SPs compliance among NSs was high, the compliance varied by year of study and was affected by the nursing staff. Furthermore, SPs compliance among NSs can be enhanced by increasing SPs knowledge, providing more SPs training, promoting management support, reducing identified SPs barriers, and improving nursing staff compliance to SPs.


title: Potential risks of SARS-Cov-2 infection on reproductive health

text: Abstract The outbreak of 2019 novel coronavirus disease (COVID-19) has been a major epidemic threat all over the world. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focused on its potential risks on reproductive health, including reproductive system and function, as well as gamete and embryo development, which was underpinned by the virus, drugs, chemical disinfectants and panic psychology during the outbreak of COVID-19.