title: Hydroxychloroquine-induced Stevens–Johnson syndrome in COVID-19: a rare case report

text: The international outbreak of respiratory illness termed coronavirus disease 2019 (COVID-19) began in December 2019 that has affected >0.8 million individuals. Self-limiting respiratory tract involvement, severe pneumonia, multiorgan failure and death are the spectrum of COVID-19. To date, there are no especial therapeutic agents for COVID-19 infections. One such medication includes the antimalarial hydroxychloroquine (HCQ), which recently reported as a possible therapy for shortening the duration of COVID-19 symptoms, reducing inflammatory reactions to infection, impairing the exacerbation of pneumonia and boosting lung imaging findings. Like all medications, HCQ has side effects and may occur in COVID-19 patients. Here, we report on the case of a 42-year-old woman, presented with fever and dry cough, who had COVID-19 and 2 days later presented with a pruritic erythematous maculopapular rash, which started from the distal of upper extremities and rapidly, involved the entire body.


title: Waste Not, Want Not: Re-Usability of N95 Masks

text: As the spread of COVID-19 illnesses continues to escalate amidst a substandard supply of protective equipment for health care providers, the question of extended use or reuse of N95 masks has emerged. As well, the relative effectiveness of the N95 compared to other mask types have been entertained. A recent article by Abd-Elsayed and Karri aim to put these topics into focus. Additionally, personal correspondence between Drs. Richard Prielipp (University of Minnesota Department of Anesthesiology) and Peter Tsai (inventor of the N95 mask) offers perspectives on managing the reuse of this central element of protective equipment.


Silent War to Emerging or Re-emerging Respiratory Infection Diseases Badly Kept in Mind


title: Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity

text: Porcine reproductive and respiratory syndrome virus (PRRSV) induces a weak immune response enabling it to persist in different organs of infected pigs. This has been attributed to the ability of PRRSV to influence the induction of cytokine responses. In this study, we investigated the cytokine transcriptional profiles in different compartments of the mediastinal lymph node of pigs infected with three genotype 1 PRRSV strains of differing pathogenicity: the low virulence prototype Lelystad virus (LV), and UK field strain 215–06 and the highly virulent subtype 3 SU1-Bel isolate from Belarus. We have used a combination of laser capture micro-dissection (LCM) followed by real time quantitative PCR (RT-qPCR) and immunohistochemical (IHC) detection of immune cell markers (CD3, CD79a and MAC387) and RT-qPCR quantification of PRRSV and cytokine transcripts. Compared to mock infected pigs, we found a significant downregulation of TNF-α and IFN-α in follicular and interfollicular areas of the mediastinal lymph node from 3 days post-infection (dpi) in animals infected with all three strains. This was accompanied by a transient B cell depletion and T cell and macrophage infiltration in the follicles together with T cell depletion in the interfollicular areas. A delayed upregulation of IFN-γ and IL-23p19 was observed mainly in the follicles. The PRRSV load was higher in all areas and time-points studied in the animals infected with the SU1-Bel strain. This paper describes the first application of LCM to study the cytokine transcript profiles and virus distribution in different compartments of the lymph node of pigs.


title: Memory T-cell competition for bone marrow seeding

text: The presence in the bone marrow of memory CD8 T cells is well recognized. However, it is still largely unclear how T-cell migration from the lymphoid periphery to the bone marrow is regulated. In the present report, we show that antigen-specific CD4 T cells, as well as antigen-specific CD8 T cells, localize to the bone marrow of immunized mice, and are sustained there over long periods of time. To investigate the rules governing T-cell migration to the bone marrow, we generated chimeric mice in which the lymphoid periphery contained two genetically or phenotypically distinct groups of T cells, one of which was identical to the host. We then examined whether a distinct type of T cell had an advantage over the others in the colonization of bone marrow. Our results show that whereas ICAM1 and CD18 molecules are both involved in homing to lymph nodes, neither is crucial for T-cell bone marrow colonization. We also observed that memory-phenotype CD44(high) T cells, but not virgin-type CD44(−/low) T cells, preferentially home to the bone marrow upon adoptive transfer to normal young mice, but not to thymectomized old recipients where an existing memory T-cell pool precludes their free access. Thus, T-cell colonization of the bone marrow uses distinct molecules from those implicated in lymph node homing, and is regulated both by the properties of the T cell and by the competitive efficacy of other T cells inhabiting the same, saturable niche. This implies that the homing potential of an individual lymphocyte is not merely an intrinsic property of the cell, but rather a property of the lymphoid system taken as a whole.


title: Potential challenges of employing a formal environmental scanning approach in hospitality organizations

text: Most previous studies on environmental scanning (ES) in the field of hospitality management suggest that hospitality organizations establish formal systematic ES procedures and have a freestanding ES unit to identify opportunities and threats in their external environment. However, some serious criticisms have been raised in the field of strategic management against the employment of such a formal and systematic approach to ES. These opposing views have rarely been discussed in the hospitality management literature. The aim of this paper, therefore, is to bring these views to the fore in the process of reviewing previous research into ES, and to discuss the major challenges involved for hospitality organizations in employing such a formal approach to ES. The discussion throughout this paper reveals that ES is essential for every organization; however, it is even more complex and difficult to accomplish than portrayed in most previous studies in the hospitality management field. The paper identifies and discusses major challenges and problems in employing a form ES approach in hospitality organizations. It also provides recommendations about how ES activities can best be carried out in complex and dynamic environments.


title: Biomimetic nanoparticles as universal influenza vaccine

text: Abstract Pandemic virus infections, such as seasonal influenza, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pose a major public health threat globally. 1 , 2 Much effort has been devoted to suppress the virus, including vaccine prevention, autoimmunity enhancement, and anti-virus drugs treatment. Among these strategies, development of novel and improved vaccine technologies attracts broad attention as they can nip the virus outbreak in the bud and avoid the appearance of public health emergency. Therefore, Wang et al. 1 recently offer a promising means: they develop universal viral vaccine through biomimetic nanoparticles.


title: Secondary Syphilis with Pleural Effusion: Case Report and Literature Review

text: Here we present a case of a 38-year-old Indian man with a history of extramarital relationships who presented with pleurisy, skin rash, and radiological findings of pleural effusion. After thorough investigation of the etiology of his acute illness, he was found to be positive for syphilis. Review of literature revealed a small number of case reports of pleural effusion as a manifestation of secondary syphilis. The review of criteria proposed in the literature was utilized to diagnose this patient as a case of pulmonary syphilis.


title: Rapid community-driven development of a SARS-CoV-2 tissue simulator

text: The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors like diabetes. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interactions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving rapid refinements with a two-to-four week release cycle. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health.


title: Prevalence of and Risk Factors Associated With Mental Health Symptoms Among the General Population in China During the Coronavirus Disease 2019 Pandemic

text: IMPORTANCE: People exposed to coronavirus disease 2019 (COVID-19) and a series of imperative containment measures could be psychologically stressed, yet the burden of and factors associated with mental health symptoms remain unclear. OBJECTIVE: To investigate the prevalence of and risk factors associated with mental health symptoms in the general population in China during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This large-sample, cross-sectional, population-based, online survey study was conducted from February 28, 2020, to March 11, 2020. It involved all 34 province-level regions in China and included participants aged 18 years and older. Data analysis was performed from March to May 2020. MAIN OUTCOMES AND MEASURES: The prevalence of symptoms of depression, anxiety, insomnia, and acute stress among the general population in China during the COVID-19 pandemic was evaluated using the Patient Health Questionnaire–9, Generalized Anxiety Disorder–7, Insomnia Severity Index, and Acute Stress Disorder Scale. Logistic regression analyses were used to explore demographic and COVID-19–related risk factors. RESULTS: Of 71 227 individuals who clicked on the survey link, 56 932 submitted the questionnaires, for a participation rate of 79.9%. After excluding the invalid questionnaires, 56 679 participants (mean [SD] age, 35.97 [8.22] years; 27 149 men [47.9%]) were included in the study; 39 468 respondents (69.6%) were aged 18 to 39 years. During the COVID-19 pandemic, the rates of mental health symptoms among the survey respondents were 27.9% (95% CI, 27.5%-28.2%) for depression, 31.6% (95% CI, 31.2%-32.0%) for anxiety, 29.2% (95% CI, 28.8%-29.6%) for insomnia, and 24.4% (95% CI, 24.0%-24.7%) for acute stress. Participants with confirmed or suspected COVID-19 and their family members or friends had a high risk for symptoms of depression (adjusted odds ratios [ORs], 3.27 [95% CI, 1.84-5.80] for patients; 1.53 [95% CI, 1.26-1.85] for family or friends), anxiety (adjusted ORs, 2.48 [95% CI, 1.43-4.31] for patients; 1.53 [95% CI, 1.27-1.84] for family or friends), insomnia (adjusted ORs, 3.06 [95% CI, 1.73-5.43] for patients; 1.62 [95% CI, 1.35-1.96] for family or friends), and acute stress (adjusted ORs, 3.50 [95% CI, 2.02-6.07] for patients; 1.77 [95% CI, 1.46-2.15] for family or friends). Moreover, people with occupational exposure risks and residents in Hubei province had increased odds of symptoms of depression (adjusted ORs, 1.96 [95% CI, 1.77-2.17] for occupational exposure; 1.42 [95% CI, 1.19-1.68] for Hubei residence), anxiety (adjusted ORs, 1.93 [95% CI, 1.75-2.13] for occupational exposure; 1.54 [95% CI, 1.30-1.82] for Hubei residence), insomnia (adjusted ORs, 1.60 [95% CI, 1.45-1.77] for occupational exposure; 1.20 [95% CI, 1.01-1.42] for Hubei residence), and acute stress (adjusted ORs, 1.98 [95% CI, 1.79-2.20] for occupational exposure; 1.49 [95% CI, 1.25-1.79] for Hubei residence). Both centralized quarantine (adjusted ORs, 1.33 [95% CI, 1.10-1.61] for depression; 1.46 [95% CI, 1.22-1.75] for anxiety; 1.63 [95% CI, 1.36-1.95] for insomnia; 1.46 [95% CI, 1.21-1.77] for acute stress) and home quarantine (adjusted ORs, 1.30 [95% CI, 1.25-1.36] for depression; 1.28 [95% CI, 1.23-1.34] for anxiety; 1.24 [95% CI, 1.19-1.30] for insomnia; 1.29 [95% CI, 1.24-1.35] for acute stress) were associated with the 4 negative mental health outcomes. Being at work was associated with lower risks of depression (adjusted OR, 0.85 [95% CI, 0.79-0.91]), anxiety (adjusted OR, 0.92 [95% CI, 0.86-0.99]), and insomnia (adjusted OR, 0.87 [95% CI, 0.81-0.94]). CONCLUSIONS AND RELEVANCE: The results of this survey indicate that mental health symptoms may have been common during the COVID-19 outbreak among the general population in China, especially among infected individuals, people with suspected infection, and people who might have contact with patients with COVID-19. Some measures, such as quarantine and delays in returning to work, were also associated with mental health among the public. These findings identify populations at risk for mental health problems during the COVID-19 pandemic and may help in implementing mental health intervention policies in other countries and regions.


title: Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread

text: Skin infection with the poxvirus vaccinia (VV) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. Given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. To better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mRNA expression levels after epicutaneous (ec.) VV infection and found a large increase the anti-inflammatory cytokine IL-10. Ex vivo analyses revealed that T cells in the skin were the primary IL-10-producing cells. To understand the distribution of IL-10-producing T cells in vivo, we performed multiphoton intravital microscopy (MPM) of VV-infected mice, assessing the location and dynamic behavior of IL-10 producing cells. Although virus-specific T cells were distributed throughout areas of the inflamed skin lacking overt virus-infection, IL-10(+) cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific CD8(+) T cells. Paradoxically, neutralizing secreted IL-10 in vivo with an anti-IL-10 antibody increased viral lesion size and viral replication. Additional analyses demonstrated that IL-10 antibody administration decreased recruitment of CCR2(+) inflammatory monocytes, which were important for reducing viral burden in the infected skin. Based upon these findings, we conclude that spatially concentrated IL-10 production limits cutaneous viral replication and dissemination, likely through modulation of the innate immune repertoire at the site of viral growth.


title: Multimonth Dispensing of Antiretroviral Therapy Protects the Most Vulnerable From 2 Pandemics at Once

text: We encourage governments in countries that have a high prevalence of people living with HIV to implement multimonth dispensing of antiretroviral therapy to safeguard both patients with HIV and health care workers from coronavirus disease 2019.


title: Engineering targeted viral vectors for gene therapy

text: To achieve therapeutic success, transfer vehicles for gene therapy must be capable of transducing target cells while avoiding impact on non-target cells. Despite the high transduction efficiency of viral vectors, their tropism frequently does not match the therapeutic need. In the past, this lack of appropriate targeting allowed only partial exploitation of the great potential of gene therapy. Substantial progress in modifying viral vectors using diverse techniques now allows targeting to many cell types in vitro. Although important challenges remain for in vivo applications, the first clinical trials with targeted vectors have already begun to take place.


title: Viruses are frequently present as the infecting agent in acute exacerbations of chronic obstructive pulmonary disease in patients presenting to hospital

text: BACKGROUND: Viral causes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are well recognised but only recently have rapid tests become available. AIMS: To identify respiratory viruses in the general population and those associated with hospitalisation in AECOPD using polymerase chain reaction (PCR) on nasopharyngeal aspirate (NPA), and the relationship between symptoms, viral detection and inflammatory markers. METHODS: A review of viruses detected in the general population in a health district between August 2014 and July 2015, using multiplex PCR for viruses from NPA samples. In addition, a single hospital, retrospective audit of patients admitted with suspected AECOPD was conducted. RESULTS: Of the 8811 NPA tested, 5599 (64%) were positive for at least one virus and 2069 of these were obtained from adults. In adults, the most common viruses identified were Influenza A (31%), Rhinovirus (27%) and respiratory syncytial virus A/B (10%). Most patients with AECOPD (102 of 153) had NPA sent for viral PCR testing and 59 (58%) were positive. The most common viruses identified were Influenza A (31%), Rhinovirus (24%) and respiratory syncytial virus A/B (17%) with co‐infecting bacteria cultured in 22 sputum samples. Patients with influenza‐like symptoms were more likely to have a positive viral PCR than those without symptoms (P < 0.004). The median C‐reactive protein on admission was lower in the virus‐infected than uninfected AECOPD (28 vs 60 mg/L, P < 0.026). CONCLUSION: The spectrum of viruses detected in patients with AECOPD is similar to that of the general population. Viruses are more likely to be identified in patients with AECOPD who present with influenza‐like symptoms and a low C‐reactive protein.


title: Respiratory disease in pregnancy

text: Abstract A variety of respiratory complications can be encountered in pregnancy. An understanding of the pathophysiology of pregnancy is important in the management of such complications. Despite the changes in immunity, the incidence of respiratory infections is not higher in pregnancy. Asthma is the most common preexisting medical disorder encountered in pregnancy, and its prevalence in women of childbearing age is increasing. There is a slight increase in the risk to the pregnancy, but suboptimal therapy is the most common reason for poor control. X-rays should be obtained whenever clinically indicated, and most drugs used in the management of asthma have a long track record of safety. For women with poor control in pregnancy, there should be good liaison between the respiratory physician and the obstetrician. Tuberculosis is increasingly important and may complicate human immunodeficiency virus infection. First-line antituberculous drugs can safely be administered in pregnancy and lactation.


title: Transient virus infection and multiple sclerosis

text: Multiple sclerosis (MS) is a chronic, demyelinating disease of the CNS in which autoimmunity to myelin plays a role in pathogenesis. The epidemiology of MS indicates that it may be triggered by a virus infection before the age of adolescence, but attempts to associate a specific virus with MS have produced equivocal results. Many studies of the aetiology of MS have postulated that a persistent virus infection is involved, but transient virus infection may provide a plausible alternative mechanism that could explain many of the inconsistencies in MS research. The most studied animal model of MS is chronic relapsing experimental autoimmune encephalomyelitis (CREAE), which is induced in susceptible animals following injection of myelin components. While CREAE cannot provide information on the initiating factor for MS, it may mimic disease processes occurring after an initial trigger that may involve transient virus infection. The disease process may comprise separate triggering and relapse phases. The triggering phase may involve sensitisation to myelin antigens as a result of damage to oligodendrocytes or molecular mimicry. The relapse phase could be similar to CREAE, or alternatively relapses may be induced by further transient virus infections which may not involve infection of the CNS, but which may involve the recrudescence of anti‐myelin autoimmunity. Although current vaccines have a high degree of biosafety, it is suggested that the measles‐mumps‐rubella vaccine in particular could be modified to obviate any possibility of triggering anti‐myelin autoimmunity. Copyright © 2000 John Wiley & Sons, Ltd.


title: The carboxyl-terminal part of the putative Berne virus polymerase is expressed by ribosomal frameshifting and contains sequence motifs which indicate that toro- and coronaviruses are evolutionarily related.

text: Sequence analysis of the 3' part (8 kb) of the polymerase gene of the torovirus prototype Berne virus (BEV) revealed that this area contains at least two open reading frames (provisionally designated ORF1a and ORF1b) which overlap by 12 nucleotides. The complete sequence of ORF1b (6873 nucleotides) was determined. Like the coronaviruses, BEV was shown to express its ORF1b by ribosomal frameshifting during translation of the genomic RNA. The predicted tertiary RNA structure (a pseudoknot) in the toro- and coronaviral frameshift-directing region is similar. Analysis of the amino acid sequence of the predicted BEV ORF1b translation product revealed homology with the ORF1b product of coronaviruses. Four conserved domains were identified: the putative polymerase domain, an area containing conserved cysteine and histidine residues, a putative helicase motif, and a domain which seems to be unique for toro- and coronaviruses. The data on the 3' part of the polymerase gene of BEV supplement previously observed similarities between toro- and coronaviruses at the level of genome organization and expression. The two virus families are more closely related to each other than to other families of positive-stranded RNA viruses.


title: Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation

text: Over the past several decades, significant advances have been made in identifying factors that contribute to the pathogenesis of multiple sclerosis (MS) and have culminated in the approval of some effective therapeutic strategies for disease intervention. However, the mechanisms by which environmental factors, such as infection, contribute to the pathogenesis and/or symptom exacerbation remain to be fully elucidated. Relapse frequency in MS patients contributes to neurological impairment and, in the initial phases of disease, serves as a predictor of poor disease prognosis. The purpose of this review is to examine the evidence that supports a role for peripheral infection in modulating the natural history of this disease. Evidence supporting a role for infection in promoting exacerbation in animal models of MS is also reviewed. Finally, a few mechanisms by which infection may exacerbate symptoms of MS and other neurological diseases are discussed. Those who comprise the majority of MS patients acquire approximately two upper-respiratory infections per year; furthermore, this type of infection doubles the risk for MS relapse, underscoring the contribution of this relationship as being potentially important and particularly detrimental.


title: Chapter 5 Laboratory Diagnosis of Viral Infections

text: Publisher Summary Specific diagnoses of a viral infection are described in this chapter that are generally of five types: those that demonstrate the presence of infectious virus; those that detect viral antigens; those that detect viral nucleic acids; those that demonstrate the presence of an agent-specific antibody response; and those that directly visualize the virus. Most available routine tests are agent dependent—that is, they are designed to detect a specific virus and will give a negative test result even if other viruses are present in the sample. For this reason, agent-independent tests such as virus isolation and electron microscopy are still used to identify the unexpected or unknown agent in a clinical sample. Traditional methods such as virus isolation are still widely used; however, many are too slow to have any direct influence on the clinical management of an index case. For some economically important viruses, standardized diagnostic tests and reagents of good quality are available commercially; assays have been miniaturized to conserve reagents and decrease costs; instruments have been developed to automate tests, again often decreasing costs; and computerized analyses aid in making the interpretation of results as objective as possible in addition to facilitating reporting, record keeping, and billing. Respiratory diseases, diarrheal diseases of neonates, and some mucocutaneous diseases may be caused by a variety of different infectious agents, including viruses. Rapid and accurate identification of the causative agent can be the basis for establishing a management plan that prevents additional losses in the stable, kennel, flock, or herd.


title: Sports balls as potential SARS-CoV-2 transmission vectors

text: Abstract Objects passed from one player to another have not been assessed for their ability to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the surface of sport balls, notably a football, tennis ball, golf ball, and cricket ball could not harbour inactivated virus when it was swabbed onto the surface, even for 30 seconds. However, when high concentrations of 5,000 dC/mL and 10,000 dC/mL are directly pipetted onto the balls, it could be detected after for short time periods. Sports objects can only harbour inactivated SARS-CoV-2 under specific, directly transferred conditions, but wiping with a dry tissue or moist ‘baby wipe’ or dropping and rolling the balls removes all detectable viral traces. This has helpful implications to sporting events.


title: A leguminous trypsin-chymotrypsin inhibitor Limenin with antifungal activity from Phaseolus limensis

text: A trypsin-chymotrypsin inhibitor, designated Limenin, with both antifungal and antibacterial activity, and exhibiting a molecular mass of 18.0 kDa in SDS–polyacrylamide gel electrophoresis, was isolated from the large lima bean (Phaseolus limensis) legumes by a combination of extraction, ammonium sulfate precipitation, ion exchange chromatography on SP-Toyopearl and high performance liquid chromatography (HPLC) on Mono S. The isoelectric point was estimated to be 7.6 by isoelectric focusing. The 15 N-terminal amino acid sequences were determined to be DFVIDNEGNPLENGG, demonstrating some resemblance to those other protease inhibitors and inhibitor precursors from leguminous plants. It exerted potent antifungal action toward Botrytis cinerea, Alternaria alternata(Fr.) Keissl, and Pythium aphanidermatum. It showed antiproliferative activity toward tumor cells including human liver hepatoma cells Bel-7402 and neuroblastoma cells SHSY5Y. However, it had no effect on bacteria Staphylococcus aureus and Salmonella.


title: Artificial Intelligence and COVID-19: A Multidisciplinary Approach

text: The COVID-19 pandemic is taking a colossal toll in human suffering and lives. A significant amount of new scientific research and data sharing is underway due to the pandemic which is still rapidly spreading. There is now a growing amount of coronavirus related datasets as well as published papers that must be leveraged along with artificial intelligence (AI) to fight this pandemic by driving news approaches to drug discovery, vaccine development, and public awareness. AI can be used to mine this avalanche of new data and papers to extract new insights by cross-referencing papers and searching for patterns that AI algorithms could help discover new possible treatments or help in vaccine development. Drug discovery is not a trivial task and AI technologies like deep learning can help accelerate this process by helping predict which existing drugs, or brand-new drug-like molecules could treat COVID-19. AI techniques can also help disseminate vital information across the globe and reduce the spread of false information about COVID-19. The positive power and potential of AI must be harnessed in the fight to slow the spread of COVID-19 in order to save lives and limit the economic havoc due to this horrific disease.


title: Air ventilation assessment under unstable atmospheric stratification — A comparative study for Hong Kong

text: Abstract In most current air ventilation assessment (AVA) studies, a simple neutral assumption that does not consider thermal effects is adopted, particularly for numerical simulation practices. With statistics of daytime observations during summer in Hong Kong as an example, this study demonstrates that neutral atmospheric boundary conditions occur with a very low probability, which implies that current practices are indeed far away from reality. This study is devoted to addressing this knowledge gap by cross-comparisons of field measurements, wind tunnel tests, and large-eddy simulations (LES) under neutral and unstable conditions. It is found that LES-computed velocity ratios under unstable conditions are in line with field measurements, while results of simulations under neutral conditions are close to those of wind tunnel tests. Enhanced vertical mixing due to surface heating produces improved ventilation performance in the unstable case. The neutral assumption tends to underestimate pedestrian-level velocity ratios compared to a diabatic condition; hence it is deemed conservative when it is adopted in AVA practices. Moreover, stronger wind direction variance under unstable conditions results in weaker correlation between velocity ratios and frontal area indices than neutral conditions, which implies that street orientations become less important in ventilation under unstable conditions.


title: Responding to Hospital System and Student Curricular Needs: COVID‐19 Student Service Corps

text: Throughout March 2020, cases of COVID‐19 grew exponentially, and New York emerged as an epicenter of the crisis. Social distancing, shortages of personal protective equipment, and clinical care needs necessitated that students be removed from the clinical setting. A group of students, faculty members, and administrators formed to identify ways in which students could be involved in supporting the health system.


title: Coronavirus jolts labs to warp speed

text: To thwart SARS-CoV-2, labs hurry to hone assays, swap findings and share resources.


A life immersed in science


title: Lack of MERS Coronavirus Neutralizing Antibodies in Humans, Eastern Province, Saudi Arabia

text: We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.


title: Ecohealth research in Southeast Asia: past, present and the way forward

text: Ecohealth is a comprehensive approach to understanding health at its human, animal and environmental interface in a socio-ecological systems context. This approach was introduced widely in Southeast Asia (SEA) by the Canadian International Development Research Centre (IDRC) in the late 2000s. Aimed at addressing the problem of emerging infectious diseases (EIDs), numerous such projects and activities have been generated throughout the region. Ecohealth is increasingly converging with the One Health approach, as both movements emphasise a holistic understanding to health. We conducted a scoping review by considering all of the Ecohealth programmes, initiatives and projects that have been implemented in SEA since the introduction of the approach, and also gathered information from peer-reviewed literature. The objective of this paper is to review Ecohealth activities within SEA over the last 10 years to address the lessons learned, challenges faced and the way forward for Ecohealth in the region. Activities range from those focusing purely on capacity, projects focusing on research and projects covering both. Achievements to date include, for example, research contributing to the field of infectious diseases in relation to social ecological factors and associated urbanisation and agricultural intensification. Challenges remain at the project design and implementation level, in the available capacity and coordination to develop Ecohealth research teams in the countries, gauging teams’ assimilation of Ecohealth’s underlying tenets and their translation into sustainable disease prevention and control, as well as in the ability to scale up Ecohealth projects. We suggest that the way forward for Ecohealth should be from a regional perspective in terms of research, training and policy translation using Ecohealth in combination with the One Health approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-4-5) contains supplementary material, which is available to authorized users.


title: Discovery of Potential M2 Channel Inhibitors Based on the Amantadine Scaffold via Virtual Screening and Pharmacophore Modeling

text: The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession number GQ385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.


El genoma humano. Límites y perspectivas en el avance de la medicina


title: Replication of respiratory viruses, particularly influenza virus, rhinovirus, and coronavirus in HuH7 hepatocarcinoma cell line

text: Detection of viral antigens and isolation methods has long been used for the diagnosis of respiratory virus infections. The objective was to determine the ability of HuH7 cells to support the replication of prototype and wild strains of respiratory viruses. The cell culture‐adapted strains of influenza viruses A and B, parainfluenza viruses 1–4, respiratory syncytial viruses A and B, both strains of the human metapneumoviruses, numerous rhinoviruses, most of the adenoviruses, coronaviruses 229E and OC43, and a number of enteroviruses (poliovirus type 3, coxsackie virus B1, echovirus type 30) replicate in HuH7. The kinetic study of the replication of influenza A and B viruses showed that there were infected cells in HuH7 and MDCK lines as early as 24 hr post‐infection. However, the replication of influenza A and B viruses was more rapid and intense on MDCK cells than on HuH7 cells. During the three winters of 1999–2000, 2000–2001, and 2001–2002, of the 1,226 (23.3%) direct fluorescent assay‐positive nasal aspirates from children admitted to hospital, 788 were positive for respiratory syncytial virus, 228 for influenza virus, 133 for parainfluenza virus, and 77 for adenovirus. Of the 4,032 direct fluorescent assay‐negative nasal aspirates, 571 virus isolates were identified by using HuH7 cell culture; 272 rhinoviruses, 100 influenza viruses A and B, 85 enteroviruses, 40 adenoviruses, 35 coronaviruses, 31 parainfluenza viruses, and 10 respiratory syncytial viruses. Interestingly, 100/328 (30.5%) influenza viruses A and B, 40/189 (21.1%) adenoviruses, and 31/164 (19%) parainfluenza viruses type 1–3, not detected by direct fluorescent assay, were identified by isolation in HuH7 cell culture. J. Med. Virol. 77:295–301, 2005. © 2005 Wiley‐Liss, Inc.


Macrophages at the Fork in the Road to Health or Disease


title: Deletion Variants of Middle East Respiratory Syndrome Coronavirus from Humans, Jordan, 2015

text: We characterized Middle East respiratory syndrome coronaviruses from a hospital outbreak in Jordan in 2015. The viruses from Jordan were highly similar to isolates from Riyadh, Saudi Arabia, except for deletions in open reading frames 4a and 3. Transmissibility and pathogenicity of this strain remains to be determined.


title: Fetuin-A deficiency is associated with infantile cortical hyperostosis (Caffey disease)

text: BACKGROUND: Infantile cortical hyperostosis (ICH)/Caffey disease is an inflammatory collagenopathy of infancy, manifested by subperiosteal bone hyperplasia. Genetically, ICH was linked with heterozygosity for an R836C mutation in the COL1A1 gene. Although an autosomal-recessive trait is also suspected, it has not been proven thus far. METHODS: A case of an infant male born to consanguineous parents is reported, presenting with classical findings, course, and clinical outcome of ICH. Whole-exome sequencing (WES) was performed in order to identify a possible underlying genetic defect. RESULTS: WES analysis revealed a novel homozygous nonsense mutation in lysine 2 of fetuin-A, encoded by the ALPHA-2-HS-GLYCOPROTEIN (AHSG) gene (c.A4T; p.K2X). Fetuin-A is an important regulator of bone remodeling and an inhibitor of ectopic mineralization. By enzyme-linked immunosorbent assay (ELISA), we show a complete deficiency of this protein in the patient’s serum, compared to controls. CONCLUSION: A novel homozygous nonsense mutation in AHSG gene has been found in ICH patient with a typical phenotype, resulting in fetuin-A deficiency. This finding postulates an autosomal-recessive mode of inheritance in ICH, which, unlike the autosomal-dominant inheritance associated with COL1A1, is associated with AHSG and fetuin-A deficiency.


A case series of Novel-Coronavirus infection in heart transplantation from two centers in the pandemic area in the North of Italy


title: Chilblain‐like lesions during COVID‐19 epidemic: a preliminary study on 63 patients

text: We have recently noticed an outbreak of chilblain-like lesions in Italy contemporarily to COVID-19 epidemic. Due to the well known lockdown-related difficulties to visit the patients1 we created a Google form aimed to collect information about patients presenting with these singular clinical findings. An easy to access and quick tool was chosen by the investigators in order to permit the other colleagues to spend the least amount of time, given the severe health emergency.


title: Influence of Obesity on Pneumococcus Infection Risk in the Elderly

text: Obesity negatively affects immune function and host defense mechanisms. Obesity is associated with chronic activation of the innate immune system and consequent local and systemic inflammation which contribute to pathologic conditions such as type-2 diabetes mellitus, cancer, psoriasis, atherosclerosis, and inflammatory bowel disease. Individuals with obesity have increased susceptibility to contract viral, bacterial, and fungal infections and respond sub-optimally to vaccination. In this review, we summarize research findings on the effects of obesity on immune responses to respiratory tract infections (RTI), focusing on Streptococcus pneumoniae (“pneumococcus”) infection, which is a major cause of morbidity and mortality in the US, causing community-acquired infections such as pneumonia, otitis media and meningitis. We show that the risk of infection is higher in elderly individuals and also in individuals of certain ethnic groups, although in a few reports obesity has been associated with better survival of individuals admitted to hospital with pneumococcus infection, a phenomenon known as “obesity paradox.” We discuss factors that are associated with increased risk of pneumococcal infection, such as recent infection with RTI, chronic medical conditions, and immunosuppressive medications.


title: Potential for global spread of a novel coronavirus from China

text: An epidemic of a novel coronavirus emerged from Wuhan, China, in late December 2019 and has since spread to several large Chinese cities. Should a scenario arise where this coronavirus spreads more broadly across China, we evaluate how patterns of international disease transmission could change.


title: 4 Cleaning and Disinfecting Gastrointestinal Endoscopy Equipment

text: Abstract Outbreaks of infection transmission due to contaminated flexible endoscopes have focused the attention of health care personnel, senior management, device manufacturers, and regulators on the need to improve the approach used to offer this valuable service. This chapter presents the principles of flexible endoscope reprocessing along with a pragmatic approach to the judicious selection and proper reprocessing of endoscopic equipment, as well as guidance for prevention and management of infection transmission inclusive of newer sterilization (e.g., hydrogen peroxide vapor) and disinfection (e.g., improved hydrogen peroxide) technologies. It also provides an outline of the Quality Systems approach that is applicable to flexible endoscope reprocessing and the need for ongoing staff competency and audits of endoscope cleaning, disinfection, and storage practices. Furthermore, the most current regulatory, expert organization, and manufacturer's recommendations are reviewed.


title: Pilgrims and MERS-CoV: what’s the risk?

text: The risk of Middle East Respiratory Syndrome Coronavirus spreading globally is worrying, given the annual mass gathering of the Hajj and the year-long influx of pilgrims undertaking the Umrah. Based on the incidence in Saudi Arabia since June 2012, the most likely scenario given recent pilgrim numbers is estimated to be one case per Hajj, and three Umrah pilgrims per year, but which could plausibly reach seven and ten pilgrims respectively. In addition to the 2015 Hajj, national surveillance systems should be on the alert for the low but long-lasting risk of infected pilgrims returning from the Umrah throughout the year.


Celebrity, Pandemic, and Domesticity


Association of nausea with buprenorphine analgesia for rats


title: Identification of Pathogens by Mass Spectrometry

text: Background: Mass spectrometry (MS) is a suitable technology for microorganism identification and characterization. Content: This review summarizes the MS-based methods currently used for the analyses of pathogens. Direct analysis of whole pathogenic microbial cells using MS without sample fractionation reveals specific biomarkers for taxonomy and provides rapid and high-throughput capabilities. MS coupled with various chromatography- and affinity-based techniques simplifies the complexity of the signals of the microbial biomarkers and provides more accurate results. Affinity-based methods, including those employing nanotechnology, can be used to concentrate traces of target microorganisms from sample solutions and, thereby, improve detection limits. Approaches combining amplification of nucleic acid targets from pathogens with MS-based detection are alternatives to biomarker analyses. Many data analysis methods, including multivariate analysis and bioinformatics approaches, have been developed for microbial identification. The review concludes with some current clinical applications of MS in the identification and typing of infectious microorganisms, as well as some perspectives. Summary: Advances in instrumentation (separation and mass analysis), ionization techniques, and biological methodologies will all enhance the capabilities of MS for the analysis of pathogens.


title: Improved clinical and economic outcomes in severe bronchiolitis with pre-emptive nCPAP ventilatory strategy

text: PURPOSE: Severe bronchiolitis is the leading cause of admission to the pediatric intensive care unit (PICU). Nasal continuous positive airway pressure (nCPAP) has become the primary respiratory support, replacing invasive mechanical ventilation (MV). Our objective was to evaluate the economic and clinical consequences following implementation of this respiratory strategy in our unit. METHODS: This was a retrospective cohort analysis of 525 infants with bronchiolitis requiring respiratory support and successively treated during two distinct periods with invasive MV between 1996 and 2000, P1 (n = 193) and nCPAP between 2006 and 2010, P2 (n = 332). Costs were estimated using the hospital cost billing reports. RESULTS: Patients’ baseline characteristics were similar between the two periods. P2 is associated with a significant decrease in the length of ventilation (LOV) (4.1 ± 3.5 versus 6.9 ± 4.6 days, p < 0.001), PICU length of stay (LOS) (6.2 ± 4.6 versus 9.7 ± 5.5 days, p < 0.001) and hospital LOS. nCPAP was independently associated with a shorter duration of ventilatory support than MV (hazard ratio 1.8, 95 % CI 1.5–2.2, p < 0.001). nCPAP was also associated with a significant decrease in ventilation-associated complications, and less invasive management. The mean cost of acute viral bronchiolitis-related PICU hospitalizations was significantly decreased, from 17,451 to 11,205 € (p < 0.001). Implementation of nCPAP led to a reduction of the total annual cost of acute viral bronchiolitis hospitalizations of 715,000 €. CONCLUSION: nCPAP in severe bronchiolitis is associated with a significant improvement in patient management as shown by the reduction in invasive care, LOV, PICU LOS, hospital LOS, and economic burden.


title: Emergence of Blue Sky Over Delhi Due to Coronavirus Disease (COVID-19) Lockdown Implications

text: Due to coronavirus pandemic (COVID-19) prevailing in more than 210 countries, out of them only few have promulgated lockdown and on March 24, 2020 India also implemented lockdown for 21 days to prevent the community spread of virus among people. Since then, lockdown heavily restricts travel movements of flights, rail, intercity bus services besides industrial activity halt throughout the country. The significant improvement in the air quality of Delhi region was observed due to strict implementation of lockdown. During the lockdown period, improvement in ambient air quality helped us in circumventing the coronavirus community spread. The preliminary results showing the decrease in horizontal advection of pollutants has given an opportunity to understand the background concentrations of air pollutants over Delhi. To analyse this peculiar situation, we have assessed the pollutants datasets collected by twelve different online ambient air quality monitoring stations (AQMS) of Central Pollution Control Board (CPCB), New Delhi, India and observed a colossal improvement in the ambient air quality. The analysis of data confirms the sharp decline in concentrations (nearly 200%) of PM(2.5) and PM(10). The concentration of nitrous oxides (NO(x)), recorded its maximum (342 ppb) on 12 January 2020 in CRRI–Mathura Road, Delhi with the lowest value as 24 ppb on 30 March 2020 (reduced to nearly 14 times of the peak value). In the triad of this infectious disease, the role of environment is not linked better however, the ground reality cannot be ignored due to environment around us receives, maintains, protects and transports the aetiological agents to host prevailing in polluted environment which makes our lungs more susceptible to viral attacks. Therefore, a cleaner environment would prove to be an effective measure to halt and reduce the transmission of viral infections.


title: Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins

text: Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors. Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined. Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain. By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity. Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection. The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved. Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains. These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.


title: Epidemic Influenza Seasons from 2008 to 2018 in Poland: A Focused Review of Virological Characteristics

text: The objective of this review was to elaborate on changes in the virological characteristics of influenza seasons in Poland in the past decade. The elaboration was based on the international influenza surveillance system consisting of Sentinel and non-Sentinel programs, recently adopted by Poland, in which professionals engaged in health care had reported tens of thousands of cases of acute upper airway infections. The reporting was followed by the provision of biological specimens collected from patients with suspected influenza and influenza-like infection, in which the causative contagion was then verified with molecular methods. The peak incidence of influenza infections has regularly been in January–March each epidemic season. The number of tested specimens ranged from 2066 to 8367 per season from 2008/2009 to 2017/2018. Type A virus predominated in nine out of the ten seasons and type B virus of the Yamagata lineage in the 2017/2018 season. Concerning the influenza-like infection, respiratory syncytial virus predominated in all the seasons. There was a sharp increase in the proportion of laboratory confirmations of influenza infection from season to season in relation to the number of specimens examined, from 3.2% to 42.4% over the decade. The number of confirmations, enabling a prompt commencement of antiviral treatment, related to the number of specimens collected from patients and on the virological situation in a given season. Yet influenza remains a health scourge, with a dismally low yearly vaccination rate, which recently reaches just about 3.5% of the general population in Poland.


title: Virus Life Cycle

text: Viruses are obligate intracellular parasites. Viruses must gain entry into target cells and usurp the host cellular machinery to produce a progeny virus. The multiple steps involved in the virus propagation occurring inside cells are collectively termed the “virus life cycle.” After entering the cell and localizing to an intracellular milieu, the virus sheds its capsid, transcribes its RNA, translates its RNA to the viral proteins, replicates its genome, assembles the viral components, and finally exits from the cell. Here, the steps involved in the virus life cycle are described with emphasis on entry and exit.


title: Modalités pratiques de prise en charge des patients apnéiques par l’ORL durant l’épidémie de COVID-19

text: Résumé La prise en charge des pathologies du sommeil a été fortement impactée par l’épidémie de COVID-19. La reprise des soins auprès de la population, à la sortie du confinement, va nécessiter des précautions visant à limiter les risques de contamination des patients et des soignants. L’Association Française du Sommeil en ORL (AFSORL) et la Société Française d’ORL (SFORL) proposent dans ce document une synthèse des mesures permettant la poursuite de la prise en charge du syndrome d’apnées du sommeil dans ces nouvelles conditions d’exercice. L’accent est mis sur la téléconsultation, les modalités d’enregistrement nocturne, les conditions de traitement par ventilation en pression positive continue (PPC) et le report des thérapeutiques plus invasives.


title: Echocardiographic Findings in Covid-19 Pneumonia

text: The aim of this study was to characterize the echocardiographic phenotype of patients with Covid-19 pneumonia and its relation to biomarkers. Seventy-four patients (59±13 years, 78% male) admitted with Covid-19 were included after referral for transthoracic echocardiography (TTE) as part of routine care. A level 1 British Society of Echocardiography TTE assessed chamber size and function, valvular disease and likelihood of pulmonary hypertension. The chief abnormalities were right ventricular (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and CRP levels. In contrast, left ventricular (LV) function was hyper-dynamic or normal in most (89%) patients.


title: Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection

text: BACKGROUND: Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. RESULTS: In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. CONCLUSION: In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.


Arbeiten am Limit


title: COVID-19 and Hypertension: The Role of ACE2 and the Renin-Angiotensin System

text: ABSTRACT Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of SARS-CoV-2, the virus responsible for COVID-19, into host cells. Since RAS inhibitors have been suggested to increase ACE2 expression, healthcare providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.


title: Potential T-cell and B-cell Epitopes of 2019-nCoV

text: As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data. The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.


title: Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses

text: Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg (null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD. Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab, indicating induction of antigen-specific B cells in the NOG-dKO mice. Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells, indicating the induction of antigen-specific T cells in the NOG-dKO mice. Adoptive cell therapies (ACTs) using melanoma antigen recognized by T cells (MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells. ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice, in which changes in human cancer phenotypes by immune intervention, such as increased CD271 expression, could be evaluated. Therefore, NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.


title: Indoor air quality and human health: Truth vs mass hysteria

text: Indoor air quality is an important issue, because anything we breathe can potentially affect our health. To determine if there is a real health risk, well-designed scientifically valid studies must be performed. Although much attention has focused on sick building syndrome, chemical sensitivities, and mycotoxicosis, there actually is very little evidence that these conditions have an adverse effect on human health. In contrast, real health issues have been shown to exist regarding indoor air triggers of allergies and asthma. Outdoor allergens are difficult to avoid because the pollen grains we encounter outdoors, which are the size that can cause allergies, are windborne and can travel for miles. However, indoor allergens can cause severe allergic symptoms and may also have a priming effect on an individual’s susceptibility to simultaneous or subsequent exposure of other outdoor allergens. Therefore, it is important to minimize exposure to indoor allergens. Determination of individual susceptibility can be paired with knowledge of the patient’s indoor exposure pattern to produce a customized management plan of avoidance, which can be used in conjunction with pharmacological treatment of allergies and asthma, as well as immunotherapy.


title: An analysis of the health status of the United Arab Emirates: the ‘Big 4’ public health issues

text: BACKGROUND: The United Arab Emirates (UAE) is a rapidly developing country composed of a multinational population with varying educational backgrounds, religious beliefs, and cultural practices, which pose a challenge for population-based public health strategies. A number of public health issues significantly contribute to morbidity and mortality in the UAE. This article summarises the findings of a panel of medical and public health specialists from UAE University and various government health agencies commissioned to report on the health status of the UAE population. METHODS: A systematic literature search was conducted to retrieve peer-reviewed articles on health in the UAE, and unpublished data were provided by government health authorities and local hospitals. RESULTS: The panel reviewed and evaluated all available evidence to list and rank (1=highest priority) the top four main public health issues: 1) Cardiovascular disease accounted for more than 25% of deaths in 2010; 2) Injury caused 17% of mortality for all age groups in 2010; 3) Cancer accounted for 10% of all deaths in 2010, and the incidence of all cancers is projected to double by 2020; and 4) Respiratory disorders were the second most common non-fatal condition in 2010. CONCLUSION: The major public health challenges posed by certain personal (e.g. ethnicity, family history), lifestyle, occupational, and environmental factors associated with the development of chronic disease are not isolated to the UAE; rather, they form part of a global health problem, which requires international collaboration and action. Future research should focus on population-based public health interventions that target the factors associated with the development of various chronic diseases.


title: Protective Effect of Intranasal Regimens Containing Peptidic Middle East Respiratory Syndrome Coronavirus Fusion Inhibitor Against MERS-CoV Infection

text: To gain entry into the target cell, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) uses its spike (S) protein S2 subunit to fuse with the plasma or endosomal membrane. Previous work identified a peptide derived from the heptad repeat (HR) 2 domain in S2 subunit, HR2P, which potently blocked MERS-CoV S protein–mediated membrane fusion. Here, we tested an HR2P analogue with improved pharmaceutical property, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo. HR2P-M2 was highly effective in inhibiting MERS-CoV S protein–mediated cell-cell fusion and infection by pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region. It interacted with the HR1 peptide to form stable α-helical complex and blocked six-helix bundle formation between the HR1 and HR2 domains in the viral S protein. Intranasally administered HR2P-M2 effectively protected adenovirus serotype-5–human dipeptidyl peptidase 4–transduced mice from infection by MERS-CoV strains with or without mutations in the HR1 region of S protein, with >1000-fold reduction of viral titers in lung, and the protection was enhanced by combining HR2P-M2 with interferon β. These results indicate that this combination regimen merits further development to prevent MERS in high-risk populations, including healthcare workers and patient family members, and to treat MERS-CoV–infected patients.


title: Diffuse parenchymal lung disease as first clinical manifestation of GATA-2 deficiency in childhood

text: BACKGROUND: GATA-2 transcription factor deficiency has recently been described in patients with a propensity towards myeloid malignancy associated with other highly variable phenotypic features: chronic leukocytopenias (dendritic cell-, monocyto-, granulocyto-, lymphocytopenia), increased susceptibility to infections, lymphatic vasculature abnormalities, and sensorineural deafness. Patients often suffer from opportunistic respiratory infections; chronic pulmonary changes have been found in advanced disease. CASE PRESENTATION: We present a case of a 17-year-old previously healthy Caucasian male who was admitted to the hospital with fever, malaise, headache, cough and dyspnea. A chest X-ray revealed bilateral interstitial infiltrates and pneumonia was diagnosed. Despite prompt clinical improvement under antibiotic therapy, interstitial changes remained stable. A high resolution computer tomography showed severe diffuse parenchymal lung disease, while the patient’s pulmonary function tests were normal and he was asymptomatic. Lung tissue biopsy revealed chronic reparative and resorptive reaction with organizing vasculitis. At the time of the initial presentation to the hospital, serological signs of acute infection with Epstein-Barr virus (EBV) were present; EBV viremia with atypical serological response persisted during two-year follow up. No other infectious agents were found. Marked monocytopenia combined with B-cell lymphopenia led to a suspicion of GATA-2 deficiency. Diagnosis was confirmed by detection of the previously published heterozygous mutation in GATA2 (c.1081 C > T, p.R361C). The patient’s brother and father were both carriers of the same genetic defect. The brother had no clinically relevant ailments despite leukocyte changes similar to the index patient. The father suffered from spondylarthritis, and apart from B-cell lymphopenia, no other changes within the leukocyte pool were seen. CONCLUSION: We conclude that a diagnosis of GATA-2 deficiency should be considered in all patients with diffuse parenchymal lung disease presenting together with leukocytopenia, namely monocyto-, dendritic cell- and B-lymphopenia, irrespective of severity of the clinical phenotype. Genetic counseling and screening for GATA2 mutations within the patient’s family should be provided as the phenotype is highly variable and carriers without apparent immunodeficiency are still in danger of developing myeloid malignancy. A prompt recognition of this rare condition helps to direct clinical treatment strategies and follow-up procedures.


title: Aspirin Intolerance: Experimental Models for Bed-to-Bench

text: Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.


title: Chapter 15 Functionalized carbon nanotubes and their promising applications in therapeutics and diagnostics

text: Abstract Carbon nanotubes (CNTs) have attracted much attention from researchers worldwide in recent years due to their high aspect ratio, high surface area, and excellent material properties, such as electrical and thermal conductivities and mechanical strength. These rolled-up seamless cylinders of graphene sheets possess nanosized hollow-tube-shaped structures. The CNTs can be single-walled, double-walled or multi-walled, depending upon the number of graphene layers from which a single nanotube is composed. The CNTs, favoring encapsulation of drug molecules or by possible attachment of theranostic agents on the nanotube walls, have enabled their use in controlled drug delivery, and in targeting of drug molecules to specific sites such as the lymphatic system, brain, ocular system, and cancerous tissue. This chapter provides an overview of various types of CNTs, methods utilized for their commercial production, and the functionalization approaches employed in drug-delivery applications. In addition, the chapter also endeavors to provide a thoughtful insight into the toxicity and regulatory concerns that need to be addressed before the CNTs can be launched in the market.


title: Insomnia during COVID-19 pandemic and lockdown: Prevalence, severity, and associated risk factors in France population

text: In response to Voitsidis et al. (2020) published in Psychiatry Research addressing the paucity of research on insomnia during a pandemic, we obtained data from an online cross-sectional survey by documenting the prevalence of clinical insomnia and its contributing factors in a French general public sample. Participants (N= 556) completed the Insomnia Severity Index, UCLA Loneliness scale, and provided information on sociodemographics, antecedents of mental and physical health conditions, and COVID-19-related stressful life events. In our sample, 19.1% met the diagnostic criteria of clinical insomnia, which was twice lower than that reported in Voitsidis et al., but close to those found among Chinese and Italian populations. We confirmed COVID-19-related worries and loneliness to be the major contributing factors to clinical insomnia, in addition to education status, being infected by the virus and pre-existing mental health illness. These findings underscore that sleep-related problems should be an important component of mental health interventions during pandemics.


title: Individualized prediction nomograms for disease progression in mild COVID‐19

text: The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic rapidly. The majority of COVID‐19 patients are with mild syndromes. This study aimed to develop models for predicting disease progression in mild cases. The risk factors for the requirement of oxygen support in mild COVID‐19 were explored using multivariate logistic regression. Nomogram as visualization of the models was developed using R software. A total of 344 patients with mild COVID‐19 were included in the final analysis, 45 of whom progressed and needed high‐flow oxygen therapy or mechanical ventilation after admission. There were 188 (54.7%) males, and the average age of the cohort was 52.9 ± 16.8 years. When the laboratory data were not included in multivariate analysis, diabetes, coronary heart disease, T ≥ 38.5℃ and sputum were independent risk factors of progressive COVID‐19 (Model 1). When the blood routine test was included the CHD, T ≥ 38.5℃ and neutrophil‐to‐lymphocyte ratio were found to be independent predictors (Model 2). The area under the receiver operator characteristic curve of model 2 was larger than model 1 (0.872 vs 0.849, P = .023). The negative predictive value of both models was greater than 96%, indicating they could serve as simple tools for ruling out the possibility of disease progression. In conclusion, two models comprised common symptoms (fever and sputum), underlying diseases (diabetes and coronary heart disease) and blood routine test are developed for predicting the future requirement of oxygen support in mild COVID‐19 cases.


title: Intimate partner violence crisis in the COVID-19 pandemic: how can radiologists make a difference?

text: • The COVID-19 crisis resulted in a variety of physical and mental health issues beyond the viral infection itself, as indicated by an increase in domestic violence. • Radiologists should be aware of typical intimate partner violence (IPV) injury patterns, actively ask potential IPV victims about the cause of injury, and be familiar with support systems for IPV victims of their institutions. • Emergency and radiology departments should review their protocols for identifying and supporting IPV victims, and train their staff to work together to implement these measures during and beyond the COVID-19 crisis.


Meta-analysis is not always the best way to round out a systematic review: a few thoughts prompted by the COVID-19 pandemic and “spiced-up” with an earthquake


title: Large Eddy Simulation of Air Escape through a Hospital Isolation Room Single Hinged Doorway—Validation by Using Tracer Gases and Simulated Smoke Videos

text: The use of hospital isolation rooms has increased considerably in recent years due to the worldwide outbreaks of various emerging infectious diseases. However, the passage of staff through isolation room doors is suspected to be a cause of containment failure, especially in case of hinged doors. It is therefore important to minimize inadvertent contaminant airflow leakage across the doorway during such movements. To this end, it is essential to investigate the behavior of such airflows, especially the overall volume of air that can potentially leak across the doorway during door-opening and human passage. Experimental measurements using full-scale mock-ups are expensive and labour intensive. A useful alternative approach is the application of Computational Fluid Dynamics (CFD) modelling using a time-resolved Large Eddy Simulation (LES) method. In this study simulated air flow patterns are qualitatively compared with experimental ones, and the simulated total volume of air that escapes is compared with the experimentally measured volume. It is shown that the LES method is able to reproduce, at room scale, the complex transient airflows generated during door-opening/closing motions and the passage of a human figure through the doorway between two rooms. This was a basic test case that was performed in an isothermal environment without ventilation. However, the advantage of the CFD approach is that the addition of ventilation airflows and a temperature difference between the rooms is, in principle, a relatively simple task. A standard method to observe flow structures is dosing smoke into the flow. In this paper we introduce graphical methods to simulate smoke experiments by LES, making it very easy to compare the CFD simulation to the experiments. The results demonstrate that the transient CFD simulation is a promising tool to compare different isolation room scenarios without the need to construct full-scale experimental models. The CFD model is able to reproduce the complex airflows and estimate the volume of air escaping as a function of time. In this test, the calculated migrated air volume in the CFD model differed by 20% from the experimental tracer gas measurements. In the case containing only a hinged door operation, without passage, the difference was only 10%.


title: Enhanced cell fusion activity in porcine epidemic diarrhea virus adapted to suckling mice

text: Porcine epidemic diarrhea virus (PEDV) is the major causative agent of fatal diarrhea in piglets. To study the pathogenic features of PEDV using a mouse model, PEDV with virulence in mice is required. In pursuit of this, we adapted a tissue-culture-passed PEDV MK strain to suckling mouse brains. PEDV obtained after ten passages through the brains (MK-p10) had increased virulence for mice, and its fusion activity in cultured cells exceeded that of the original strain. However, the replication kinetics of MK and MK-p10 did not differ from each other in the brain and in cultured cells. The spike (S) protein of MK-p10 had four amino acid substitutions relative to the original strain. One of these (an H-to-R substitution at residue 1,381) was first detected in PEDV isolated after eight passages, and both this virus (MK-p8) and MK-p10 showed enhanced syncytium formation relative to the original MK strain and viruses isolated after two, four, and six passages, suggesting the possibility that the H-to-R mutation was responsible for this activity. This mutation could be also involved in the increased virulence of PEDV observed for MK-p10.


title: Managing cancer during a pandemic

text: Clinicians and researchers are rapidly adapting to working in the midst of a pandemic. Herein, we share our initial thoughts of the consequences of COVID-19 for the oncology community.


title: Type I IFN Signaling Is Dispensable during Secondary Viral Infection

text: Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8(+) and CD4(+) memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host’s immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell’s requirement for a cytokine is highly dependent on the cell’s maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene’s impact by modulating its expression or function in a temporally-controllable manner.


title: Evaluation of serological cross-reactivity and cross-neutralization between the United States porcine epidemic diarrhea virus prototype and S-INDEL-variant strains

text: BACKGROUND: At least two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the United States (U.S. PEDV prototype and S-INDEL-variant strains). The current serological assays offered at veterinary diagnostic laboratories for detection of PEDV-specific antibody are based on the U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting weaned pigs; 3) determine if the various PEDV serological assays could detect antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS: A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study. Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3) PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera against the prototype strain reacted to and neutralized both prototype and S-INDEL-variant viruses, and the positive antisera against the S-INDEL-variant strain also reacted to and neutralized both prototype and S-INDEL-variant viruses, as examined by IFA antibody assays and VN tests. Antibodies against the two PEDV strains could be detected by all three ELISAs although detection rates varied to some degree. CONCLUSIONS: These data indicate that the antibodies against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross-neutralized both strains in vitro. The current serological assays based on U.S. PEDV prototype strain can detect antibodies against both U.S. PEDV strains.


title: Active Surveillance for Acute Respiratory Infections among Pediatric Long-Term Care Facility Staff

text: BACKGROUND: Transmission of respiratory viruses between staff and residents of pediatric long-term care facilities (pLTCFs) can occur. We assessed the feasibility of using text or email messages to perform surveillance for acute respiratory infections (ARIs) among staff. METHODS: From December 7, 2016 to May 7, 2017, 50 staff participants from two pLTCFs received weekly text or email requests to report the presence or absence of ARI symptoms. Those who fulfilled the ARI case definition (≥2 symptoms) had respiratory specimens collected to detect viruses by reverse transcriptase polymerase chain reaction assays. Pre- and post-surveillance respiratory specimens were collected to assess subclinical viral shedding. RESULTS: The response rate to weekly electronic messages was 93%. Twenty-one ARIs reported from 20 (40%) participants fulfilled the case definition. Respiratory viruses were detected in 29% (5/17) of specimens collected at symptom onset (influenza B, respiratory syncytial virus, coronavirus [CoV] 229E, rhinovirus [RV], and dual detection of CoV OC43 and bocavirus). Four participants had positive pre-surveillance (4 RV), and six had positive post-surveillance specimens (3 RV, 2 CoV NL63 and 1 adenovirus). CONCLUSIONS: Electronic messaging to conduct ARI surveillance among pLTCF staff was feasible.


title: Sepsis in the intensive care unit

text: Sepsis remains a major cause of mortality in intensive care. The past 15 years has seen a more uniform, world-wide approach to the management of sepsis, severe sepsis and septic shock with improved survival. Recognizing the early symptoms and signs of sepsis are key: the confused, hypoxic, hypotensive patient with pyrexia, tachycardia, tachypnoea and leucocytosis. Examination must include search for a source of infection and early drainage or debridement. Next to take appropriate cultures, give fluids and broad-spectrum antibiotics. If the picture does not improve over the next 6 hours step-up the treatment to include urine output monitoring, blood gases for base excess, lactate, haemoglobin and glucose. These will guide the management of vasopressors, insulin, fluids, transfusion and bicarbonate. If the hypotension persists (septic shock) the patient should be moved to intensive care. The most recent recommendations include the withdrawal of starch based colloids, dobutamine in place of dopamine and a higher threshold for the use of steroids. This should be instituted within 24 hours of the start of sepsis. Advanced care includes mechanical ventilation using the ARDSnet protocol. Prevention by screening, stopping cross infection and appropriate use of antibiotics remains the first priority.


title: NTCP and Beyond: Opening the Door to Unveil Hepatitis B Virus Entry

text: Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.


title: High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease

text: The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases, which were achieved by traditional techniques and high-throughput sequencing (HTS) techniques. HTS techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge and also provides a basis for further development of novel diagnostic markers, immunotherapies, and vaccines.


title: Mental health status of individuals with a mood-disorder during the COVID-19 pandemic in Australia: Initial results from the COLLATE project

text: BACKGROUND: Physical-distancing strategies during the coronavirus (COVID-19) pandemic may be particularly detrimental to the mental health of individuals with a pre-existing mood disorder. Data on the mental health status of these individuals during the current pandemic is sparse, and their current mental health needs unclear. METHOD: We characterised COVID-19 related lifestyle changes, primary concerns and psychological distress in n=1292 respondents self-reporting a mood disorder (either bipolar disorder or depressive disorder) and n=3167 respondents without any reported mental disorder from the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project; an Australian national survey launched on April 1(st) 2020. RESULTS: Psychological distress was heightened in the mood disorder group compared to the group with no mental disorder, with stress and depression further elevated in respondents with bipolar disorder compared to those with depressive disorder; and men with bipolar disorder having even higher levels of depression than women with bipolar disorder. Respondents with bipolar disorder were particularly concerned about financial issues associated with COVID-19 compared to those with depressive disorder and those with no mental disorder. Adverse changes to lifestyle behaviours were more prevalent in respondents with a mood disorder and linked to higher levels of distress. LIMITATIONS: Mood disorder was self-reported and was not clinically verified. CONCLUSIONS: Current psychological distress levels are elevated in individuals with mood disorder and are associated with maladaptive situational and lifestyle changes occurring in response to COVID-19.


title: Criteria heterogeneity in the diagnosis of acute bronchiolitis in Spain

text: Abstract Introduction Acute viral bronchiolitis (AB) is one of the most common respiratory diseases in infants. However, diagnostic criteria for AB are heterogeneous and not very well known. Objective To identify the diagnostic criteria for AB used by experts and clinical paediatricians in Spain. Methods Delphi study with Spanish AB experts, looking for the points of agreement about AB diagnosis. A subsequent cross-sectional study was conducted by means of an online questionnaire addressed to all Spanish paediatricians, reached through electronic mail messages sent by nine paediatric scientific societies. Descriptive and factorial analyses were carried out, looking for any association of diagnostic criteria with demographic or geographic variables, or with paediatric subspecialty. Results Agreement was reached by 40 experts in many issues (first episode of respiratory distress and high respiratory frequency, diagnosis in any season of the year, and usefulness of virus identification in making diagnosis), but opposite views were maintained on key characteristics such as the maximum age for diagnosis. The online questionnaire was completed by 1297 paediatricians. Their diagnostic criteria were heterogeneous and strongly associated with their paediatric sub-specialty. Their agreement with the Spanish expert consensus and with international standards was very poor. Conclusions Diagnostic criteria for AB in Spain are heterogeneous. These differences could cause variability in clinical practice with AB patients.


title: Counting Down the 2020 Goals for 9 Neglected Tropical Diseases: What Have We Learned From Quantitative Analysis and Transmission Modeling?

text: The control of neglected tropical diseases (NTDs) has received huge investment in recent years, leading to large reductions in morbidity. In 2012, the World Health Organization set ambitious targets for eliminating many of these diseases as a public health problem by 2020, an aspiration that was supported by donations of treatments, intervention materials, and funding committed by a broad partnership of stakeholders in the London Declaration on NTDs. Alongside these efforts, there has been an increasing role for quantitative analysis and modeling to support the achievement of these goals through evaluation of the likely impact of interventions, the factors that could undermine these achievements, and the role of new diagnostics and treatments in reducing transmission. In this special issue, we aim to summarize those insights in an accessible way. This article acts as an introduction to the special issue, outlining key concepts in NTDs and insights from modeling as we approach 2020.


title: Virological and clinical characterizations of respiratory infections in hospitalized children

text: BACKGROUND: The purpose of this study was to determine the incidence and seasonal distribution of viral etiological agents and to compare their clinical manifestations and disease severity, including single and co infections. METHODS: Multiplex reverse-transcription PCR was performed for the detection of viruses in nasopharyngeal aspirat. Disease severity was grouped using a categorization index as very mild/mild, and moderate/severe. Clinical and laboratory characteristics of hospitalized children with viral respiratory tract infection were analyzed. RESULTS: Viral pathogens were detected in 103/155 (66.5%) of patients. In order of frequency, identified pathogens were respiratory syncytial virus (32.0%), adenovirus (26.2%), parainfluenza viruses type 1–4 (19.4%), rhinovirus (18.4%), influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse with coinfections. The most common discharge diagnoses were "URTI" with or without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns. Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most remarkable finding in the patients (n=48, 53.3%), especially in patients with adenovirus (p<0.05). CONCLUSIONS: RSV and RhV were associated with higher severity of illness in hospitalized children. RSV found to account for half of LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than in other viruses. Coinfections were detected in 21 of the patients. The presence of coinfections was not associated with increased disease severity.


title: Biogenesis and Dynamics of the Coronavirus Replicative Structures

text: Coronaviruses are positive-strand RNA viruses that are important infectious agents of both animals and humans. A common feature among positive-strand RNA viruses is their assembly of replication-transcription complexes in association with cytoplasmic membranes. Upon infection, coronaviruses extensively rearrange cellular membranes into organelle-like replicative structures that consist of double-membrane vesicles and convoluted membranes to which the nonstructural proteins involved in RNA synthesis localize. Double-stranded RNA, presumably functioning as replicative intermediate during viral RNA synthesis, has been detected at the double-membrane vesicle interior. Recent studies have provided new insights into the assembly and functioning of the coronavirus replicative structures. This review will summarize the current knowledge on the biogenesis of the replicative structures, the membrane anchoring of the replication-transcription complexes, and the location of viral RNA synthesis, with particular focus on the dynamics of the coronavirus replicative structures and individual replication-associated proteins.


title: Tocilizumab, Adipokines and Severe Complications of COVID-19

text: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020 All studies reporting AIS occurrence in COVID-19 patients were included A total of 39 studies comprising 135 patients were studied The pooled incidence of AIS in COVID-19 patients from observational studies was 1 2% (54/4466) with a mean age of 63 4 ± 13 1 years The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8 Laboratory investigations revealed an elevated mean d-dimer (9 2 ± 14 8 mg/L) and fibrinogen (5 8 ± 2 0 g/L) Antiphospholipid antibodies were detected in a significant number of cases The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62 1%, 64/103), followed by multiple vascular territory (26 2%, 27/103) A high mortality rate was reported (38 0%, 49/129) We report the pooled incidence of AIS in COVID-19 patients to be 1 2%, with a high mortality rate Elevated d-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis


title: Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

text: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.