title: Chapter One The Global Dispersion of Pathogenic Microorganisms by Dust Storms and Its Relevance to Agriculture

text: Abstract Dust storms move an estimated 500–5000Tg of soil through Earth’s atmosphere every year. Dust-storm transport of topsoils may have positive effects such as fertilization of aquatic and terrestrial ecosystems and the evolution of soils in proximal and distal environments. Negative effects may include the stripping of nutrient-rich topsoils from source regions, sandblasting of plant life in downwind environments, the fertilization of harmful algal blooms, and the transport of toxins (e.g., metals, pesticides, herbicides, etc.) and pathogenic microorganisms. With respect to the long-range dispersion of microorganisms and more specifically pathogens, research is just beginning to demonstrate the quantity and diversity of organisms that can survive this type of transport. Most studies to date have utilized different assays to identify microorganisms and microbial communities using predominately culture-based, and more recently nonculture-based, methodologies. There is a clear need for international-scale research efforts that apply standardized methods to advance this field of science. Here we present a review of dust-borne microorganisms with a focus on their relevance to agronomy.


Infection control measures for homes of coronavirus disease 2019 heroes


title: Synthesis and antiviral activity of 18α-glycyrrhizic acid and its esters

text: New esters (sulfate, nicotinates, and 4-methoxycinnamate) of 18α-glycyrrhizic acid (18α-GA) were synthesized; these were D/E-trans-isomers of natural 18β-GA (GA), which is the major triterpene glycoside in the roots of Spanish licorice and Urals licorice (Glycyrrhiza glabra L. and Gl. uralensis Fisher). Changes in the stereochemistry of the GA aglycone led to significant decreases in its anti-HIV-1 activity.


title: Development of a novel clinical scoring system for on-farm diagnosis of bovine respiratory disease in pre-weaned dairy calves

text: Several clinical scoring systems for diagnosis of bovine respiratory disease (BRD) in calves have been proposed. However, such systems were based on subjective judgment, rather than statistical methods, to weight scores. Data from a pair-matched case-control study on a California calf raising facility was used to develop three novel scoring systems to diagnose BRD in preweaned dairy calves. Disease status was assigned using both clinical signs and diagnostic test results for BRD-associated pathogens. Regression coefficients were used to weight score values. The systems presented use nasal and ocular discharge, rectal temperature, ear and head carriage, coughing, and respiratory quality as predictors. The systems developed in this research utilize fewer severity categories of clinical signs, require less calf handling, and had excellent agreement (Kappa > 0.8) when compared to an earlier scoring system. The first scoring system dichotomized all clinical predictors but required inducing a cough. The second scoring system removed induced cough as a clinical abnormality but required distinguishing between three levels of nasal discharge severity. The third system removed induced cough and forced a dichotomized variable for nasal discharge. The first system presented in this study used the following predictors and assigned values: coughing (induced or spontaneous coughing, 2 points), nasal discharge (any discharge, 3 points), ocular discharge (any discharge, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C or 102.5°F, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 95.4% cases and 88.6% controls. The second presented system categorized the predictors and assigned weights as follows: coughing (spontaneous only, 2 points), mild nasal discharge (unilateral, serous, or watery discharge, 3 points), moderate to severe nasal discharge (bilateral, cloudy, mucoid, mucopurlent, or copious discharge, 5 points), ocular discharge (any discharge, 1 point), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥4. This system correctly classified 89.3% cases and 92.8% controls. The third presented system used the following predictors and scores: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥39.2°C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves were categorized “BRD positive” if their total score was ≥5. This system correctly classified 89.4% cases and 90.8% controls. Each of the proposed systems offer few levels of clinical signs and data-based weights for on-farm diagnosis of BRD in dairy calves.


title: Can’t Leave it at Home? The Effects of Personal Stress on Burnout and Salesperson Performance

text: Personal stress is a prevalent problem in a connected world. For salespeople, demands of a connected workplace have largely eliminated boundaries between personal and work life, allowing stress from personal issues to spill over into their work. Thus, problems of health, relationships, and finances are no longer “left at home” for salespeople. Rather, a less central workplace model (e.g., remote workplaces and mobile platforms) and 24/7 work expectations expand the workplace, which comingles personal and work demands. Utilizing a sample of 331 salespeople, we study personal stressors that cross boundaries into the workplace and find that they play a critical role in the formation of burnout across its dimensions, which leads to reduced salesperson performance. Our research contributes to the sales literature by investigating individual personal stressors via Job Demands and Conservation of Resources theories and offers insights for managers of salespeople that face both personal and work stress.


title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vertical Transmission in Neonates Born to Mothers With Coronavirus Disease 2019 (COVID-19) Pneumonia

text: One of seven neonates born to women with symptomatic coronavirus 2019 (COVID-19) infection tested positive for the infection and was asymptomatic.


title: The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome

text: Feline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated.


The impact of hydroxychloroquine shortages on patients with dermatological conditions during COVID‐19 pandemic


title: The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

text: Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.


title: COVID-19: Unmasking Telemedicine.

text: Abstract Telemedicine adoption has rapidly accelerated since the onset of the COVID-19 pandemic.1 Telemedicine provides increased access to medical care and helps to mitigate risk by conserving personal protective equipment and providing for social/physical distancing in order to continue to treat patients with a variety of allergic and immunologic conditions. During this time, many allergy and immunology clinicians have needed to adopt telemedicine expeditiously in their practices while studying the complex and variable issues surrounding its regulation and reimbursement. Some concerns have been temporarily alleviated since March 2020 to aid with patient care in the setting of COVID-19. Other changes are ongoing at the time of this publication. Members of the Telemedicine Work Group in the American Academy of Allergy, Asthma & Immunology (AAAAI) completed a telemedicine literature review of online and Pub Med resources through May 9, 2020 to detail Pre-COVID-19 telemedicine knowledge and outline up to date telemedicine material. This work group report was developed to provide guidance to allergy/immunology clinicians as they navigate the swiftly evolving telemedicine landscape.


title: Virus outbreak crosses boundaries

text: Summary The current outbreak of coronavirus disease COVID-19 is showing up vulnerabilities in many aspects of the globalised world we live in. The suggestion that it may have originated in the endangered pangolin also puts animal trafficking in the spotlight. The human–wildlife interface remains an important risk factor for further disease outbreaks. Michael Gross reports.


title: Ethics of instantaneous contact tracing using mobile phone apps in the control of the COVID-19 pandemic

text: In this paper we discuss ethical implications of the use of mobile phone apps in the control of the COVID-19 pandemic. Contact tracing is a well-established feature of public health practice during infectious disease outbreaks and epidemics. However, the high proportion of pre-symptomatic transmission in COVID-19 means that standard contact tracing methods are too slow to stop the progression of infection through the population. To address this problem, many countries around the world have deployed or are developing mobile phone apps capable of supporting instantaneous contact tracing. Informed by the on-going mapping of ‘proximity events’ these apps are intended both to inform public health policy and to provide alerts to individuals who have been in contact with a person with the infection. The proposed use of mobile phone data for ‘intelligent physical distancing’ in such contexts raises a number of important ethical questions. In our paper, we outline some ethical considerations that need to be addressed in any deployment of this kind of approach as part of a multidimensional public health response. We also, briefly, explore the implications for its use in future infectious disease outbreaks.


title: Prediction of receptorome for human-infecting virome

text: The virus receptor is key for viral infection of host cells. Identification of the virus receptor is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high level of N-glycosylation, high number of interaction partners and high expressions. Here, we built a random-forest model to identify human virus receptorome from human cell membrane proteins with accepted accuracy based on combination of unique features of human virus receptors and protein sequences. A total of 729 human cell membrane proteins were predicted to constitute the receptorome for the human-infecting virome. Combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies further predicted receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. Finally, we predicted the candidate alternative receptors for the 2019-nCoV. The study would greatly facilitate identification of receptors for human-infecting virome.


title: Outbreak of invasive aspergillosis in heart transplant recipients: The role of screening computed tomography scans in asymptomatic patients and universal antifungal prophylaxis

text: BACKGROUND: Delays in diagnosing pulmonary invasive aspergillosis (IA), a significant cause of morbidity and mortality among heart transplant recipients (HTRs), may impact on successful treatment. The appropriate screening strategy for IA in these patients remains undefined, particularly in the setting of nosocomial outbreaks. We describe our experience employing chest computed tomography (CT) scans as a screening method for IA. In addition, we comment on antimicrobial prophylaxis in HTRs in the setting of an outbreak. METHODS: Screening CT scans of the chest and serum galactomannan (GM) were performed in HTRs during an outbreak that followed the index case of IA. Abnormal CT findings prompted a diagnostic workup. Antimicrobial prophylaxis for new transplants recipients included intravenous micafungin while hospitalized, followed by outpatient inhaled amphotericin B for up to 3 months. RESULTS: During a 10‐month period, five cases of IA were identified among HTRs. Two additional asymptomatic patients were diagnosed with IA among 15 asymptomatic HTRs who underwent screening chest CT scans. Among the five cases of IA in HTRs, two of five (40%) had a partial response and the other three failed voriconazole therapy. Complete response to voriconazole therapy assessed at 12 weeks was achieved in these two asymptomatic HTRs diagnosed via screening CTs. Serum GM was positive only in one of the symptomatic cases. The negative predictive value of CT scans was 100% (95% confidence interval, 71.5%‐100%). CONCLUSIONS: In an outbreak setting, screening CT scans of the chest may aid in early detection of asymptomatic HTRs with IA and improve outcome.


title: Fear and trust: How risk perceptions of avian influenza affect Chinese consumers’ demand for chicken

text: Abstract This article quantifies the impact of H7N9 bird flu on chicken demand and consumer willingness to pay (WTP) in China. We measure risk perception, fear and trust against actual reduction in consumption and stated change in WTP for safe chicken between 2012 and 2013. Through a survey conducted in each year on the same Chinese urban consumers, we found that the consumption of chicken never increased after the emergence of H7N9 in 2013, and WTP for safe chicken did not necessarily increase relative to generic risks associated with consuming chicken in 2012. Factors such as the fear of H7N9's spreading, the impact of distrust (especially the distrust in government) enhanced the deviation of consumption and WTP; and the sheer mentioning of H7N9 is more important and negative than whether it was associated with a risk-perception reducing or risk-perception elevating message given to consumers.


title: Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases

text: Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.


title: The Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition

text: The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of FPRs have expanded to include additional roles in homeostasis of organ functions and modulation of inflammation. In a prototype, FPRs recognize peptides containing N-formylated methionine such as those produced in bacteria and mitochondria, thereby serving as pattern recognition receptors. The repertoire of FPR ligands, however, has expanded rapidly to include not only N-formyl peptides from microbes but also non-formyl peptides of microbial and host origins, synthetic small molecules and an eicosanoid. How these chemically diverse ligands are recognized by the three human FPRs (FPR1, FPR2 and FPR3) and their murine equivalents is largely unclear. In the absence of crystal structures for the FPRs, site-directed mutagenesis, computer-aided ligand docking and structural simulation have led to the identification of amino acids within FPR1 and FPR2 that interact with several formyl peptides. This review article summarizes the progress made in the understanding of FPR ligand diversity as well as ligand recognition mechanisms used by these receptors.


title: Epidemiology of Acute Respiratory Infections in Children in Guangzhou: A Three-Year Study

text: Acute Respiratory Infections (ARI) are some of the most common human diseases worldwide. However, they have a complex and diverse etiology, and the characteristics of the pathogens involved in respiratory infections in developing countries are not well understood. In this work, we analyzed the characteristics of 17 common respiratory pathogens in children (≤14 years old) with ARI in Guangzhou, southern China over a 3-year period using real-time polymerase chain reaction. Pathogens were identified in 2361/4242 (55.7%) patients, and the positivity rate varied seasonally. Ten of the 17 pathogens investigated showed positivity rates of more than 5%. The most frequently detected pathogens were respiratory syncytial virus (768/2361, 32.5%), influenza A virus (428/2361, 18.1%), enterovirus (138/2361, 13.3%), Mycoplasma pneumoniae (267/2361, 11.3%) and adenovirus (213/2361, 9.0%). Co-pathogens were common and found in 503 of 2361 (21.3%) positive samples. When ranked according to frequency of occurrence, the pattern of co-pathogens was similar to that of the primary pathogens, with the exception of human bocavirus, human coronavirus and human metapneumovirus. Significant differences were found in age prevalence in 10 of the 17 pathogens (p≤0.009): four basic patterns were observed, A: detection rates increased with age, B: detection rates declined with age, C: the detection rate showed distinct peaks or D: numbers of patients were too low to detect a trend or showed no significant difference among age groups (p>0.05). These data will be useful for planning vaccine research and control strategies and for studies predicting pathogen prevalence.


title: Connaissances actuelles sur la toux apparue dans un contexte bronchopulmonaire

text: Résumé La toux est très fréquente au cours de l’asthme. Elle est constante eu cours de la bronchite chronique qu’elle contribue à définir ; habituellement cette bronchite chronique est d’origine tabagique mais l’inhalation de canabis, des expositions professionnelles, la pollution domestique ou atmosphérique, peuvent également être en cause. Au cours de l’asthme et de la bronchite chronique, la toux résulte de l’inflammation et de l’hypersécrétion de la muqueuse bronchique. Chez le fumeur, la toux peut également révéler un cancer bronchique. Parmi les nombreuses autres causes de toux chronique, la dilatation des bronches est habituellement reconnue contrairement à la bronchite à éosinophiles.


title: Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells

text: Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use. Communicated by Ramaswamy H. Sarma


title: Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV

text: BACKGROUND: The spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein. RESULTS: First, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S(958-966), VLNDILSRL) induced specific CTLs both ex vivo in PBLs of healthy HLA-A2(+ )donors and in HLA-A2.1/K(b )transgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates. CONCLUSION: These results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.


title: Debate: COVID‐19 and children in India

text: The COVID‐19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world’s children amidst the pandemic which may have lasting consequences. The COVID‐19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children’s lives – their health, development, learning, behaviour and their families’ economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.


title: One Health, emerging infectious diseases and wildlife: two decades of progress?

text: Infectious diseases affect people, domestic animals and wildlife alike, with many pathogens being able to infect multiple species. Fifty years ago, following the wide-scale manufacture and use of antibiotics and vaccines, it seemed that the battle against infections was being won for the human population. Since then, however, and in addition to increasing antimicrobial resistance among bacterial pathogens, there has been an increase in the emergence of, mostly viral, zoonotic diseases from wildlife, sometimes causing fatal outbreaks of epidemic proportions. Concurrently, infectious disease has been identified as an increasing threat to wildlife conservation. A synthesis published in 2000 showed common anthropogenic drivers of disease threats to biodiversity and human health, including encroachment and destruction of wildlife habitat and the human-assisted spread of pathogens. Almost two decades later, the situation has not changed and, despite improved knowledge of the underlying causes, little has been done at the policy level to address these threats. For the sake of public health and wellbeing, human-kind needs to work better to conserve nature and preserve the ecosystem services, including disease regulation, that biodiversity provides while also understanding and mitigating activities which lead to disease emergence. We consider that holistic, One Health approaches to the management and mitigation of the risks of emerging infectious diseases have the greatest chance of success. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.


title: Homage to Prof. M.G. Replacement: A Celebration of Structural Biology at Purdue University

text: Summary On a glorious spring day in the American Midwest, friends, colleagues, collaborators, and alumni of Prof. M.G. Replacement gathered together at the campus of Purdue University, West Lafayette, Indiana to celebrate 40 years of structural biology and honor the man behind it all: M.G. Rossmann. The date also corresponded approximately to MGR’s 75th birthday. It was a memorable occasion for several reasons. An earlier meeting 10 years ago did also render homage to Michael (New Directions in Protein-Structure Relationships: Symposium in Honor of Professor M.G. Rossmann’s 65th Birthday, Purdue University, October 21, 1995), but on this occasion the symposium was much more encompassing of structural biology and had a more global character. A large number of featured speakers presented and discussed advances in vast areas of structural biology and came from the four corners of the world to share their work with the new generations of structural biologists currently being trained at Purdue University.


Proposed Changes to the Inpatient Services for the Disabled in the United States Post COVID-19: Editorial


COVID-19: losing battles or winning the war?


Risikorechner für schweren COVID-19-Verlauf


Brazilian Justice response to protect the prison population from Covid-19


title: Clinical Manifestation and Laboratory Characteristics of SARS-CoV-2 Infection in Pregnant Women

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has become a major challenge to public health in China and other countries, considering its pathogenicity across all age groups. Pregnancy is a unique physiological condition, and is characterized by altered immunity and elevated hormone levels to actively tolerate the semi-allogeneic fetus, which undergoes a sudden and substantial fluctuation during the immediate postpartum period. Changes in clinical features, laboratory characteristics, and imaging features of pregnant women during the pre-partum and post-partum periods require further elucidation. Here, we retrospectively analyzed the clinical features, laboratory characteristics, and imaging features of eight pregnant cases of SARS-CoV-2 infection during the pre-partum and post-partum periods. Our results showed that four of the eight pregnant women were asymptomatic before delivery but became symptomatic post-partum. Correspondingly, white blood cell (WBC) counts increased and lymphocyte (LYMPH) counts decreased. C-reactive protein (CRP) levels in the serum also increased to a higher level than those in general pregnancy. Therefore, it is imperative to closely monitor laboratory parameters including the WBC count, LYMPH count, and CRP, along with other imaging features in chest CT scans, to promptly prevent, diagnose, and treat a SARS-CoV-2 infection during pregnancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00227-0) contains supplementary material, which is available to authorized users.


title: Emodin inhibits current through SARS-associated coronavirus 3a protein

text: Abstract The open-reading-frame 3a of SARS coronavirus (SARS-CoV) had been demonstrated previously to form a cation-selective channel that may become expressed in the infected cell and is then involved in virus release. Drugs that inhibit the ion channel formed by the 3a protein can be expected to inhibit virus release, and would be a source for the development of novel therapeutic agents. Here we demonstrate that emodin can inhibit the 3a ion channel of coronavirus SARS-CoV and HCoV-OC43 as well as virus release from HCoV-OC43 with a K 1/2 value of about 20μM. We suggest that viral ion channels, in general, may be a good target for the development of antiviral agents.


title: Epidemiology of Necrotizing Meningoencephalitis in Pug Dogs

text: Background: Although the histopathologic features of necrotizing meningoencephalitis (NME) have been described previously, little information is available concerning the signalment, geographic distribution, seasonal onset, treatment, and survival of affected dogs. Animals: Sixty Pugs with NME and 14 contemporaneous control Pugs with other intracranial diseases (non‐NME group). Methods: Pugs that were euthanized or died because of intracranial disease were prospectively obtained. All dogs had necropsy, histopathology, and testing for various infectious diseases and were subsequently divided into NME and non‐NME groups. Signalment, geographic distribution, seasonal onset, treatment, and survival were compared between groups. Results: In Pugs with NME, median age at onset of clinical signs was 18 months (range, 4–113 months). A greater proportion of female dogs were present in the NME group (40/60) compared with the control group (6/14). Pugs with NME had a significantly lower mean weight (7.81 kg) than control Pugs (9.79 kg) (P= .012). Mean survival in Pugs with NME was 93 days (range, 1–680 days), with dogs receiving any form of treatment living significantly longer than those that were not treated (P= .003). Anticonvulsive drugs were the only treatment significantly associated with longer survival (P= .003). Conclusions and Clinical Importance: NME appears to be a common cause of intracranial signs in Pugs, based on the high proportion of NME dogs reported in this population. Pugs with NME are most commonly young adult female dogs. Although further investigation is needed to determine the optimal treatment of NME, anticonvulsive drugs appear to beneficially affect duration of survival.


In Reply: Navigating personal risk in rhinologic surgery during the COVID‐19 pandemic


title: Melanoma Screening Days During the Coronavirus Disease 2019 (COVID-19) Pandemic: Strategies to Adopt

text: Melanoma is one of the most common cancers, with an increasing incidence worldwide. Disease stage represents the most important prognosis factor; therefore, early diagnosis is essential for melanoma patients’ survival rates. Following the outbreak in China, the coronavirus disease 2019 (COVID-19) pandemic has spread all over the world and the majority of dermatological visits have been postponed. These measures could cause a delay in melanoma diagnosis and management leading to an increase of morbidity, mortality and healthcare costs. Herein we propose an alternative model of skin cancer screening and the organization of screening campaigns in order to detect malignant lesions early during this emergency period.


title: COVID‐19 and maternal pre‐eclampsia; a synopsis

text: In March 2020, the World health organization reported coronavirus disease 2019 (COVID‐19) as a pandemic.(1) Khan et al., 2020, in their systemic review about positive COVID‐19 pregnant women, showed a rate of 29.1% preterm birth and 16.4% low birth weight among their babies.(2) This increases the interest that hyper‐inflammatory state in COVID‐19 may be associated with hypoxic injury in the placenta and developing pre‐eclamptic state.


title: Immune Responses to Viruses in the CNS

text: Abstract For recovery from infection, the immune response in the central nervous system (CNS) must eliminate or control virus replication without destroying nonrenewable, essential cells. Thus, upon intracellular virus detection, the infected cell must initiate clearance pathways without triggering neuronal cell death. As a result, the inflammatory response must be tightly regulated and unique mechanisms contribute to the immune response in the CNS. Early restriction of virus replication is accomplished by the innate immune response upon activation of pattern recognition receptors in resident cells. Infiltrating immune cells enter from the periphery to clear virus. Antibodies and interferon-γ are primary contributors to noncytolytic clearance of virus in the CNS. Lymphocytes are retained in the CNS after the acute phase of infection presumably to block reactivation of virus replication.


Steroids: a therapeutic option for COVID-19 pneumonia patients with end-stage renal disease?


title: Typhlocolitis associated with Clostridium difficile ribotypes 078 and 110 in neonatal piglets from a commercial Irish pig herd

text: BACKGROUND: Clostridium difficile is a recognised cause of typhlocolitis and diarrhoea in neonatal pigs but has never been confirmed in association with pathology and disease in Irish pigs. CASE PRESENTATION: Four neonatal piglets, with a history of diarrhoea were referred to the Central Veterinary Research Laboratory, Backweston for necropsy. They were from a fully integrated, commercial pig farm with approximately 1000 sows. Three piglets had acute, superficial, erosive and suppurative typhlocolitis and the other had mild suppurative mesocolitis. Clostridium difficile (C. difficile) toxins A/B were detected using ELISA in the colonic contents from each piglet. C. difficile isolates from two of the piglets were PCR-ribotyped as 078 and an isolate from a third pig was ribotyped as 110. CONCLUSIONS: This is the first report confirming C. difficile in association with typhlocolitis in Irish pigs.


title: Semiquantitative one-step RT-PCR for simultaneous identification of human influenza and respiratory syncytial viruses

text: Abstract A multiplex reverse transcription-polymerase chain reaction (mRT-PCR) method was developed for simultaneous detection and typing/subtyping of influenza viruses A/H1, A/H3 or B, and respiratory syncytial viruses A or B, followed by DNA semiquantitation using the Agilent 2100 Bioanalyzer. Such method provides a rapid, specific and sensitive diagnostic tool for detection and semiquantification of respiratory illness specimens.


Stem-Loop 1 in the 5’ UTR of the Sars Coronavirus can Substitute for its Counterpart in Mouse Hepatitis Virus


title: Epidemiological and Clinical Characteristics of Patients With Coronavirus Disease-2019 in Shiyan City, China

text: To investigate the early epidemic of COVID-19, a total of 176 confirmed COVID-19 cases in Shiyan city, Hubei province, China were surveyed. Our data indicated that the rate of emergence of early confirmed COVID-19 cases in Hubei province outside Wuhan was dependent on migration population, and the second-generation of patients were family clusters originating from Wuhan travelers. Epidemiological investigation indicated that the reproductive number (R(0)) under containment strategies was 1.81, and asymptomatic SARS-CoV-2 carriers were contagious with a transmission rate of 10.7%. Among the 176 patients, 53 were admitted to the Renmin Hospital of Hubei University of Medicine. The clinical characteristics of these 53 patients were collected and compared based on a positive RT-PCR test and presence of pneumonia. Clinical data showed that 47.2% (25/53) of COVID-19 patients were co-infected with Mycoplasma pneumoniae, and COVID-19 patients coinfected with M. pneumoniae had a higher percentage of monocytes (P < 0.0044) and a lower neutrophils percentage (P < 0.0264). Therefore, it is important to assess the transmissibility of infected asymptomatic individuals for SARS-CoV-2 transmission; moreover, clinicians should be alert to the high incidence of co-infection with M. pneumoniae in COVID-19 patients.


title: Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

text: Human coronavirus 229E (HCoV-229E) infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. Here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein heptad repeat 1 (HR1) and heptad repeat 2 (HR2) domains, 229E-HR1P and 229E-HR2P, respectively. We found that 229E-HR1P and 229E-HR2P could interact to form a stable six-helix bundle and inhibit HCoV-229E spike protein-mediated cell-cell fusion with IC(50) of 5.7 and 0.3 µM, respectively. 229E-HR2P effectively inhibited pseudotyped and live HCoV-229E infection with IC(50) of 0.5 and 1.7 µM, respectively. In a mouse model, 229E-HR2P administered intranasally could widely distribute in the upper and lower respiratory tracts and maintain its fusion-inhibitory activity. Therefore, 229E-HR2P is a promising candidate for further development as an antiviral agent for the treatment and prevention of HCoV-229E infection.


title: Renforcement du réseau de surveillance sentinelle de la grippe au Sénégal et résultats

text: Influenza surveillance in Senegal was initially restricted to the identification of circulating strains. The network has recently been enhanced (i) to include epidemiological data from Dakar and other regions and (ii) to extend virological surveillance to other respiratory viruses. Epidemiological data from the sentinel sites is transmitted daily by mobile phone. The data include those for other febrile syndromes similar to influenza-like illnesses (ILI), corresponding to integrated approach. Also, clinical samples are randomly selected and analyzed for influenza and other respiratory viruses. There were 180,192 declared visits to the 11 sentinel sites between week 11-2012 and week 52-2013; 24% of the visits were for fever syndromes and 25% of the cases of fever syndrome were ILI. Rhinoviruses were the most frequent cause of ILI (19%), before adenoviruses (18%), enteroviruses (18%) and influenza A viruses (13%). Co-circulation and co-infection were frequent and were responsible for ILI peaks. In conclusion, it is clear that the greatest advantage of this system is the ease with which it can be implemented, thanks to the availability of mobile phones and mobile phone networks. We recommend this solution for other African countries, because it performs very well and provides rapid benefits in terms of public health decision-making.


title: Epitope based vaccine prediction for SARS-COV-2 by deploying immuno-informatics approach

text: Abstract A new virus termed SARS-COV-2 (causing COVID-19 disease) can exhibit a progressive, fatal impact on individuals. The World Health Organization (WHO) has declared the spread of the virus to be a global pandemic. Currently, there are over 1 million cases and over 100,000 confirmed deaths due to the virus. Hence, prophylactic and therapeutic strategies are promptly needed. In this study we report an epitope, ITLCFTLKR, which is biochemically fit to HLA allelic proteins. We propose that this could be used as a potential vaccine candidate against SARS-COV-2. A selected putative epitope and HLA-allelic complexes show not only better binding scores, but also RMSD values in the range of 0–1 Å. This epitope was found to have a 99.8% structural favorability as per Ramachandran-plot analysis. Similarly, a suitable range of IC50 values and population coverage was obtained to represent greater validation of T-cell epitope analysis. Stability analysis using MDWeb and half-life analysis using the ProtParam tool has confirmed that this epitope is well-selected. This new methodology of epitope-based vaccine prediction is fundamental and fast in application, ad can be economically beneficial and viable.


title: Cost-effectiveness Analysis of Hospital Infection Control Response to an Epidemic Respiratory Virus Threat

text: The outbreak of influenza A pandemic (H1N1) 2009 prompted many countries in Asia, previously strongly affected by severe acute respiratory syndrome (SARS), to respond with stringent measures, particularly in preventing outbreaks in hospitals. We studied actual direct costs and cost-effectiveness of different response measures from a hospital perspective in tertiary hospitals in Singapore by simulating outbreaks of SARS, pandemic (H1N1) 2009, and 1918 Spanish influenza. Protection measures targeting only infected patients yielded lowest incremental cost/death averted of $23,000 (US$) for pandemic (H1N1) 2009. Enforced protection in high-risk areas (Yellow Alert) and full protection throughout the hospital (Orange Alert) averted deaths but came at an incremental cost of up to $2.5 million/death averted. SARS and Spanish influenza favored more stringent measures. High case-fatality rates, virulence, and high proportion of atypical manifestations impacted cost-effectiveness the most. A calibrated approach in accordance with viral characteristics and community risks may help refine responses to future epidemics.


title: Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia

text: Not all persons infected with Middle East respiratory syndrome coronavirus (MERS-CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed.


title: Thymus transplantation for complete DiGeorge syndrome: European experience

text: BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). METHODS: Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. OBJECTIVE: We sought to confirm and extend the results previously obtained in a single center. RESULTS: Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 10(6)/L (range, 11-440 × 10(6)/L) and 200 × 10(6)/L (range, 5-310 × 10(6)/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/10(6) T cells (range, 320-8,807/10(6) T cells) and 4,184/10(6) T cells (range, 1,582-24,596/10(6) T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). CONCLUSIONS: This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.


title: Targeting the Immune System for Pulmonary Inflammation and Cardiovascular Complications in COVID-19 Patients

text: In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.


title: Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

text: The H5 subtype highly pathogenic avian influenza (HPAI) virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA) was constructed and expressed in virus-like particles (rHA VLPs) in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5) was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.


title: Control of Streptococcus pneumoniae serotype 5 epidemic of severe pneumonia among young army recruits by mass antibiotic treatment and vaccination

text: During an outbreak of severe pneumonia among new army recruits, an epidemiological investigation combined with repeated nasopharyngeal/oropharyngeal cultures from sick and healthy contacts subjects was conducted. Fifteen pneumonia cases and 19 influenza-like illness cases occurred among 596 recruits over a 4-week period in December 2005. Pneumonia attack rates reached up to 5.5%. A single pneumococcus serotype 5 clone was isolated from blood or sputum cultures in 4 patients and 30/124 (24.1%) contacts. Immunization with 23-valent polysaccharide vaccine supplemented with a 2-dose azithromycin mass treatment rapidly terminated the outbreak. Carriage rates dropped to <1%, 24 and 45 days after intervention.


title: CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo axial diffusivity

text: BACKGROUND: Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE. METHODS: C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant. RESULTS: In vivo DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of naïve and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with axial diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial diffusivity values. Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls. CONCLUSIONS: These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.


title: Field evaluation of a Mycoplasma bovis bacterin in young dairy calves

text: Abstract Mycoplasma bovis is an important cause of pneumonia, otitis media and arthritis in young dairy calves, and there is a critical need for improved preventative strategies for this pathogen. We conducted a randomized, placebo-controlled, double-blinded field trial to determine the efficacy of a commercial M. bovis vaccine for the prevention of M. bovis-associated disease in calves. Calves (n =373) on 3 Florida dairies with a history of M. bovis infection received an M. bovis bacterin or a placebo, administered subcutaneously at 3, 14 and 35 days of age. One of the herds did not experience M. bovis-associated disease; for calves in the remaining 2 herds, the incidence risk for respiratory disease, otitis media and arthritis from 3 to 90 days of age was 0.64, 0.28 and 0.02, respectively. Vaccination had no effect on the age at first treatment for M. bovis-associated disease, incidence of respiratory disease, mortality, weight gain, or nasal colonization with M. bovis in the first 90 days of life. In one herd, vaccination was associated with an increased risk of otitis media. There was no association between M. bovis-specific serum antibody titers and morbidity in vaccinated calves. Under the field conditions in this study, this vaccine was not efficacious for the prevention of M. bovis-associated disease in young dairy calves.


title: Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling

text: Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.


title: Synthesis, physicochemical and biological properties of oligonucleotides incorporated with amino-isonucleosides

text: Antisense oligonucleotides (ASONs) and siRNAs have been applied extensively for the regulation of cellular and viral gene expression, and RNAi is currently one of the most promising new approaches for anti-tumor and anti-viral therapy. In order to improve bioactivity properties and physicochemical properties of siRNA, we synthesized a novel class of ASONs II–VII incorporated with amino-isonucleoside (isoA (1) and isoA (2)) for investigation on basic physicochemical properties. Then we designed amino-isonucleoside (isoA (1), isoA (2) and isoT (1)) incorporated siRNA 2–7. Some meaningful results have been obtained from the physicochemical property experiments in ASONs. In RNAi potency experiments, we investigated RNAi potency of each strand of the siRNA. These amino-isonucleosides incorporated siRNAs showed promising bioactivity properties and had position specificity. Reduced off target effect from sense strand loading in siRNA application was observed.


title: Analysis of optimal timing of tourism demand recovery policies from natural disaster using the contingent behavior method

text: This paper examines the applicability of contingent behavior (hereafter, CB) method for analyzing dynamic processes and efficient policies in tourism demand recovery. The CB questionnaires used for this study used a hypothetical disaster situation of bird flu in Kyoto, Japan. Safety, event, visitor information, and price discounting policies were designed accordingly. Respondents were then asked about their willingness to travel time. The results showed the optimal timing for devising pertinent policies during the year. We found that the first step requires a safety information announcement, within one week, immediately after disaster site decontamination. The second step is the implementation of event information policy within 24th to 36th week after the disaster. The third step constitutes announcing visitor information within the 37th to 52nd week after the second step. The final step is the implementation of price discounting policy, until the 52nd week, immediately after the third step.


title: Survival of Respiratory Viruses on Fresh Produce

text: In addition to enteric viruses of fecal origin, emerging zoonotic viruses such as respiratory coronaviruses and influenza viruses may potentially be transmitted via contaminated foods. The goal of this study was to determine the recovery efficiencies and the survival of two respiratory viruses, namely, adenovirus 2 (Ad2) and coronavirus 229E (CoV229E), on fresh produce in comparison to the enteric poliovirus 1 (PV1). Adenovirus was recovered with efficiencies of 56.5, 31.8, and 34.8 % from lettuce, strawberries, and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6 % yet could not be recovered from strawberries. Poliovirus was recovered with efficiencies of 76.7 % from lettuce, but only 0.06 % from strawberries. For comparison purposes, the survival of Ad2, CoV229E, and PV1 was determined for periods up to 10 days on produce. The enteric PV1 survived better than both respiratory viruses on lettuce and strawberries, with only ≤1.03 log(10) reductions after 10 days of storage at 4 °C compared to CoV229E not being recovered after 4 days on lettuce and reductions of 1.97 log(10) and 2.38 log(10) of Ad2 on lettuce and strawberries, respectively, after 10 days. Nevertheless, these respiratory viruses were able to survive for at least several days on produce. There is therefore the potential for transfer to the hands and subsequently to the mucosa via rubbing the eyes or nose. In addition, some respiratory coronaviruses (e.g., severe acute respiratory syndrome coronavirus) and adenoviruses are also capable of replication in the gut and there is thus some potential for acquisition through the consumption of contaminated produce.


title: Working through the COVID-19 outbreak: Rapid review and recommendations for MSK and allied heath personnel

text: Abstract The coronavirus (COVID-19) pandemic has caused the world to undergo unprecedented change in a short space of time. This disease has devastated the economy, infringed personal freedom, and has taken a toll on healthcare systems worldwide. This review aims to highlight aspects of this pandemic with a specific emphasis on musculoskeletal work within the secondary care setting.


title: Defective rotavirus particle assembly in lovastatin-treated MA104 cells

text: Rotavirus is a non-enveloped virus that depends on cellular lipids for cell entry and associates with lipid rafts during assembly. However, the effects of cellular lipids on rotavirus assembly are still not fully understood. The present study analyzes the effects of lovastatin, an inhibitor of cholesterol biosynthesis, during rotavirus infection in MA104 cells with regard to viral growth and particle assembly. Following viral infection, a 2-log relative reduction of viral titers was observed in drug-treated cells, while viral mRNA levels in infected cells remained unaltered in both groups. Furthermore, the levels of some viral proteins in drug-treated cells were elevated. The observed discordance between the viral RNA and protein levels and the decrease in infectivity titers of viral progeny in the drug-treated cells suggested that the drug affects viral assembly, the viral proteins not being properly incorporated into virions. Transmission electron microscopic (TEM) analysis revealed that in drug-treated cells there was an increase in “empty-looking” rotavirus particles devoid of an electron-dense core as compared to the normal, electron-dense particles seen in untreated infected cells. The present study thus provides visual evidence of defective rotavirus particle assembly as a result of cholesterol depletion.


Pathogenesis of Liver injury in COVID-19


title: T84 air‐liquid interface cultures enable isolation of human bocavirus

text: Despite being frequently detected as a co-pathogen in respiratory infections, the human bocavirus has also been shown to be a major player in viral respiratory mono-infections in all age groups (1-4). However, although known since more than a decade, cultivation of the virus remains a major challenge and was so far limited to some selected laboratories, which made either use of primary air liquid interface cell cultures or not commercially available CuFi-8 cells (5, 6). This article is protected by copyright. All rights reserved.


title: Chapter 13 Maintenance Resource Management for Technical Operations

text: Abstract This chapter starts with a brief historical overview of the MRM program, presents the key findings of the research program, discusses the typical training content and the different delivery models, and their outcomes, and concludes with the review of the influence of MRM programs on the overall safety culture in Technical Operations. Maintenance resource management (MRM) or maintenance human factors (MHF) programs started with a unique, three-party research program. The aviation industry (airlines and repair stations), federal agencies (the Federal Aviation Administration (FAA) and the National Aeronautics and Space Administration (NASA)), and the academic community came together to study specific safety issues in the technical operations environment (line and base maintenance facilities, maintenance, repair, and overhaul-MRO-facilities, as well as ramp operations). The FAA and NASA funded this research, university faculty members and students conducted the research activities, and the industry partners provided access to facilities and personnel. At an international level, the FAA and NASA, Transport Canada, and United Kingdom. Civil Aviation Authority participated in another three-way partnership that enabled information sharing among the researchers, regulators, and practitioners. This chapter also reviews some of the most commonly used incident review tools and the associated taxonomies. With the increased use of structured approach to incident investigation, the use of MRM programs moved from simple awareness programs to reactive error-correction programs, and subsequently matured to proactive, error-avoidance programs, paving the way for predictive trend analysis programs. Finally, this chapter reviews the influence of MRM programs on the safety culture in technical operations and identifies some emerging opportunities for continued research and development.


title: Pathological Changes in Masked Palm Civets Experimentally Infected by Severe Acute Respiratory Syndrome (SARS) Coronavirus

text: Summary Masked palm civets are highly susceptible to infection with the severe acute respiratory syndrome coronavirus (SARS-CoV). Infected animals become less aggressive and develop pyrexia, lethargy and diarrhoea. The present study describes the spectrum of histopathological changes in the lung, spleen, lymph node, liver, small intestine, kidney and cerebrum of civets infected experimentally with SARS-CoV. In-situ hybridization (ISH) with probes specific for the RNA polymerase gene demonstrated viral RNA in the lung, small intestine and cerebrum only. In-situ labelling was employed in order to demonstrate cellular apoptosis in the cerebrum, but there was no evidence of apoptosis within the myocardium. These results indicate that SARS-CoV causes multi-organ pathology in civets, similar to that observed in human SARS patients. These parallels suggest that civets may be used as an animal model of this infection to gain insight into the pathogenesis of SARS and for evaluation of candidate vaccines and antiviral drugs.


title: Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

text: Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.


Open Letter to Insurance Companies Regarding Mandatory in Office Visit Weight Documentation in an Era of COVID-19


title: Treatment of Severe Acute Respiratory Syndrome With Glucosteroids The Guangzhou Experience

text: Study objective To investigate the efficacy and safety profiles of corticosteroid therapy in severe acute respiratory syndrome (SARS) patients. Design Four hundred one of 1,278 SARS cases treated in Guangzhou China between December 2002 and June 2003 fulfilled the diagnostic criteria issued by the World Health Organization for confirmed identification of SARS. Among them, the diagnosis of critical SARS was defined by criteria of SARS guidelines incorporated with a low oxygenation index (OI) [< 300 mm Hg]. Data of these patients retrieved from a database were retrospectively analyzed by logistic regression and Cox regression for the effect of corticosteroid therapy on death, hospitalization days, and complication presentation. Results Among the 401 SARS patients studied, 147 of 249 noncritical patients (59.0%) received corticosteroids (mean daily dose, 105.3 ± 86.1 mg) [± SD], and all survived the disease; 121 of 152 critical patients (79.6%) received corticosteroids at a mean daily dose of 133.5 ± 102.3 mg, and 25 died. Analysis of these 401 confirmed cases did not show any benefits of corticosteroid on the death rate and hospitalization days. However, when focused on 152 critical SARS cases, factors correlated with these end points indicated by univariate analysis included use of corticosteroid, age, rigor at onset, secondary respiratory infections, pulmonary rales, grading of OI, and use of invasive ventilation. After adjustment for possible confounders, treatment with corticosteroid was shown contributing to lower overall mortality, instant mortality, and shorter hospitalization stay (p < 0.05). Incidence of complications was significantly associated with the need for invasive ventilation but not with use of corticosteroids. Conclusion This Guangzhou retrospective study revealed that proper use of corticosteroid in confirmed critical SARS resulted in lowered mortality and shorter hospitalization stay, and was not associated with significant secondary lower respiratory infection and other complications.


title: SARS: Just another viral acronym?

text: Abstract Recent observations and experimental evidence have purported that a virus causes SARS, but such viruses have been isolated in only less than half of SARS patients in some studies and virologist Vincent Plummer of Winnipeg’s National Microbiology Laboratory found that indeed 1 in 5 perfectly healthy Canadians with a history of recent travel to Asia had the virus. Therfore SARS microbiologic origins remain unclear. Outbreaks of multi-drug resistant (MDR) tuberculosis and the atypical mycobacteria simulate SARS on clinical, radiologic, epidemiologic, and diagnostic laboratory grounds and it is only logical then to include them in the differential to find a definitive cause and cure for SARS.


title: Hemagglutinating Encephalomyelitis Coronavirus Infection in Pigs, Argentina

text: We describe an outbreak of vomiting, wasting, and encephalomyelitis syndrome in piglets in Argentina, caused by porcine hemagglutinating encephalomyelitis coronavirus (PHE-CoV) infection. Diagnosis was made by epidemiologic factors, pathologic features, immunohistochemistry, reverse transcription–PCR, and genomic sequencing. This study documents PHE-CoV infection in South America.


title: Serological Evidence for Multiple Strains of Canine Norovirus in the UK Dog Population

text: Noroviruses are associated with intestinal disease in humans, cows, pigs, mice, and, more recently, dogs. In 2007, the first canine norovirus (CNV) was identified and characterized in Italy. Subsequent studies have identified CNV in stools of dogs from Portugal, Greece, and the United States. To investigate the prevalence of CNV in the UK dog population, 228 canine stool samples were screened for CNV by qPCR, and 396 serum samples were screened for anti-CNV antibodies. qPCR of RNA extracted from canine stool samples did not reveal any CNV-positive samples, based on samples collected from diarrhoeic and control dogs in 2012–2013. CNV virus-like particles to three different CNV strains were produced using recombinant baculoviruses and a seroprevalence screen undertaken. Anti-CNV antibodies were identified at significant levels in canine serum; 38.1% of samples collected between 1999–2001 and 60.1% of samples collected in 2012–2013 were seropositive. The increase in seroprevalence over time (p<0.001) suggests that the CNV strains screened for are becoming more widespread. Variation in seroprevalence to different CNV strains was also identified. Two-thirds of the dogs were seropositive to a single strain, whereas the remaining third were seropositive to two or three of the strains analysed. This study has provided the first evidence that CNV is present in the UK, with seroprevalence identified to multiple circulating strains. This warrants further study and increased awareness of this recently discovered canine virus.


title: Acute respiratory distress syndrome

text: Summary Acute respiratory distress syndrome presents as hypoxia and bilateral pulmonary infiltrates on chest imaging in the absence of heart failure sufficient to account for this clinical state. Management is largely supportive, and is focused on protective mechanical ventilation and the avoidance of fluid overload. Patients with severe hypoxaemia can be managed with early short-term use of neuromuscular blockade, prone position ventilation, or extracorporeal membrane oxygenation. The use of inhaled nitric oxide is rarely indicated and both β2 agonists and late corticosteroids should be avoided. Mortality remains at approximately 30%.


title: HIV-1 protease inhibition potential of functionalized polyoxometalates

text: Polyoxometalates (POMs) are interesting biomedical agents due to their versatile anticancer and antiviral properties, such as remarkable anti-HIV activity. Although POMs are tunable and easily accessible inorganic drug prototypes in principle, their full potential can only be tapped by enhancing their biocompatibility, for example, through organic functionalization. We have therefore investigated the HIV-1 protease inhibition potential of functionalized Keggin- and Dawson-type POMs with organic side chains. Their inhibitory performance was furthermore compared to other POM types, and the buffer dependence of the results is discussed. In addition, chemical shift mapping NMR experiments were performed to exclude POM–substrate interactions. Whereas the introduction of organic side chains into POMs is a promising approach in principle, the influence of secondary effects on the reaction system also merits detailed investigation.


title: A continuous method for the large-scale extraction of plasmid DNA by modified boiling lysis

text: This protocol describes a streamlined method of plasmid DNA extraction by continual thermal lysis, a modification of the basic boiling lysis technique, to simplify the processing of large volumes of Escherichia coli cultures. Fermented bacteria are harvested using a hollow fiber-membrane module and pre-treated with lysozyme prior to passing through a thermal exchange coil set at 70 °C to lyse the cells, and into a juxtaposed cooling coil on ice. The lysed and cooled bacteria are subsequently separated from the lysate by centrifugation and plasmid DNA is precipitated from the supernatant for further purification. The use of peristaltic pumps and two heating coils at constant temperature without the use of centrifugation enable the lysis process to become constant and controllable, providing a flow-through protocol for cell lysis and plasmid DNA extraction. Large volumes of bacterial cultures (20 l) can be processed in 2 h, yielding approximately 100 mg plasmid DNA l(−1) culture, making this an attractive protocol for consistent and large-scale preparation of plasmid DNA.


title: Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant

text: Rhinoviruses are commonly detected in symptomatic and asymptomatic children prior to HCT. Unlike pre‐HCT detection of other respiratory viruses, it is not known whether RV detection, with or without clinical symptoms, is associated with worse outcomes in children post‐HCT. In a retrospective study of children undergoing allogeneic HCT from January 2009 to February 2015, 91 children underwent allogeneic HCT, and 62 children had RPP testing within 30 days pre‐HCT. Fifty‐six (90%) children had either no pathogen (n = 34, 55%) or single RV detection (n = 22, 35%), which was the most common pathogen identified. Compared with virus negative children, children with pre‐HCT RV detection were not more likely to require ventilated support and did not have longer length of stay, higher mortality, or less days alive and out of the hospital within the first 100 days post‐HCT. In a secondary analysis of all 56 patients with RPP testing and no pathogen or RV alone detected, the seven children with LRTI had less days alive and out of the hospital within the first 100 days post‐HCT compared with the 49 children who were either asymptomatic or had URTI (10 vs 60 days, P = 0.002). In a bootstrapped regression model, presence of LRTI, not RV detection, was significantly associated with decreased days alive and out of the hospital within the first 100 days post‐HCT. Thus, pre‐HCT detection of RV, without associated LRTI, does not always warrant HCT delay.


title: Detection of novel members, structure–function analysis and evolutionary classification of the 2H phosphoesterase superfamily

text: 2′,3′ Cyclic nucleotide phosphodiesterases are enzymes that catalyze at least two distinct steps in the splicing of tRNA introns in eukaryotes. Recently, the biochemistry and structure of these enzymes, from yeast and the plant Arabidopsis thaliana, have been extensively studied. They were found to share a common active site, characterized by two conserved histidines, with the bacterial tRNA-ligating enzyme LigT and the vertebrate myelin-associated 2′,3′ phosphodiesterases. Using sensitive sequence profile analysis methods, we show that these enzymes define a large superfamily of predicted phosphoesterases with two conserved histidines (hence 2H phosphoesterase superfamily). We identify several new families of 2H phosphoesterases and present a complete evolutionary classification of this superfamily. We also carry out a structure– function analysis of these proteins and present evidence for diverse interactions for different families, within this superfamily, with RNA substrates and protein partners. In particular, we show that eukaryotes contain two ancient families of these proteins that might be involved in RNA processing, transcriptional co-activation and post-transcriptional gene silencing. Another eukaryotic family restricted to vertebrates and insects is combined with UBA and SH3 domains suggesting a role in signal transduction. We detect these phosphoesterase modules in polyproteins of certain retroviruses, rotaviruses and coronaviruses, where they could function in capping and processing of viral RNAs. Furthermore, we present evidence for multiple families of 2H phosphoesterases in bacteria, which might be involved in the processing of small molecules with the 2′,3′ cyclic phosphoester linkages. The evolutionary analysis suggests that the 2H domain emerged through a duplication of a simple structural unit containing a single catalytic histidine prior to the last common ancestor of all life forms. Initially, this domain appears to have been involved in RNA processing and it appears to have been recruited to perform various other functions in later stages of evolution.


title: Preface – Emerging Viruses: From Early Detection to Intervention

text: In the last decades, several viruses emerged, as the consequence of cross-species passage from animal reservoirs to human being. Emerging infections always represent a significant challenge for public health system as knowledge about specific pathogens are generally little while and no/few effective interventions are available. In this volume we explored special aspects of emerging infectious diseases including: the application of the theory of focality of diseases to infective syndrome; the human-animal inter-face focusing on influenza; the role of bats as main reservoir of emerging and novel human pathogens; Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemiology and clinical presentation; immediate impact on human health of the last Zika virus outbreak occurred in Pacific Ocean and the Americas; the role and potential application of animal models for the study of emerging infections, to improve disease knowledge and for developing therapeutic drugs during ongoing outbreak.


Managing diabetes in Qatar during the COVID-19 pandemic


title: miR-21a-5p Contributes to Porcine Hemagglutinating Encephalomyelitis Virus Proliferation via Targeting CASK-Interactive Protein1 In vivo and vitro

text: Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that can cause nervous symptoms in piglets with muscle tremors, hind limb paralysis, and nystagmus. Whether some factors affect virus replication and proliferation had not been fully understood in the course of nerve damage caused by PHEV infection. In recent years, some reports suggested that miRNA might play a key regulatory role in viral infection. In this study, we found the miR-21a-5p is notably up-regulated in the brains of mice and N2a cells infected with PHEV, and it down-regulated the expression of CASK-interactive protein1 (Caskin1) by directly targeting the 3′-UTR of Caskin1 using a Dual-Luciferase reporter assay. The over-expression of miR-21a-5p or Caskin1 knockdown in the host significantly contributes to PHEV proliferation. Conversely, the silencing of miR-21a-5p by miR-21a-5p inhibitors suppressed the virus proliferation. Taken together, our results indicate that Caskin1 is the direct target gene of miR-21a-5p, and it is advantageous to virus proliferation by down-regulating Caskin1. These findings may help in the development of strategies for therapeutic applications.


title: Introduction of a Novel Swine-Origin Influenza A (H1N1) Virus into Milwaukee, Wisconsin in 2009

text: On 17 April 2009, novel swine origin influenza A virus (S-OIV) cases appeared within the United States. Most influenza A diagnostic assays currently utilized in local clinical laboratories do not allow definitive subtype determination. Detailed subtype analysis of influenza A positive samples in our laboratory allowed early confirmation of a large outbreak of S-OIV in southeastern Wisconsin (SEW). The initial case of S-OIV in SEW was detected on 28 April 2009. All influenza A samples obtained during the 16 week period prior to 28 April 2009, and the first four weeks of the subsequent epidemic were sub typed. Four different multiplex assays were employed, utilizing real time PCR and end point PCR to fully subtype human and animal influenza viral components. Specific detection of S-OIV was developed within days. Data regarding patient demographics and other concurrently circulating viruses were analyzed. During the first four weeks of the epidemic, 679 of 3726 (18.2%) adults and children tested for influenza A were identified with S-OIV infection. Thirteen patients (0.34%) tested positive for seasonal human subtypes of influenza A during the first two weeks and none in the subsequent 2 weeks of the epidemic. Parainfluenza viruses were the most prevalent seasonal viral agents circulating during the epidemic (of those tested), with detection rates of 12% followed by influenza B and RSV at 1.9% and 0.9% respectively. S-OIV was confirmed on day 2 of instituting subtype testing and within 4 days of report of national cases of S-OIV. Novel surge capacity diagnostic infrastructure exists in many specialty and research laboratories around the world. The capacity for broader influenza A sub typing at the local laboratory level allows timely and accurate detection of novel strains as they emerge in the community, despite the presence of other circulating viruses producing identical illness. This is likely to become increasingly important given the need for appropriate subtype driven anti-viral therapy and the potential shortage of such medications in a large epidemic.


title: Modelling the evolution of COVID-19 in high-incidence European countries and regions: Estimated number of infections and impact of past and future intervention measures

text: A previously developed mechanistic model of COVID-19 transmission has been adapted and applied here to study the evolution of the disease and the effect of intervention measures in some European countries and territories where the disease has had a major impact. A clear impact of the major intervention measures on the reproduction number (Rt) has been found in all studied countries and territories, as already suggested by the drop in the number of deaths over time. Interestingly, the impact of such major intervention measures seems to be the same in most of these countries. The model has also provided realistic estimates of the total number of infections, active cases and future outcomes. While the predictive capabilities of the model are much more uncertain before the peak of the outbreak, we could still reliably predict the evolution of the disease after a major intervention by assuming the subsequent reproduction number from the current study. A greater challenge is to foresee the long-term impact of softer intervention measures, but this model can estimate the outcome of different scenarios and help to plan changes for the implementation of control measures in a given country or region.


title: Phenobarbital-induced anticonvulsant hypersensitivity syndrome in a cat

text: In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-year-old, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.


title: China Tuberculosis Policy at Crucial Crossroads: Comparing the Practice of Different Hospital and Tuberculosis Control Collaboration Models Using Survey Data

text: BACKGROUND: Currently three hospital and tuberculosis (TB) collaboration models exist in China: the dispensary model where TB has to be diagnosed and treated in TB dispensaries, the specialist model where TB specialist hospital also treat TB patients, and the integrated model where TB diagnosis and treatment is integrated into a general hospital. The study compared effects of the three models through exploring patient experience in TB diagnosis and treatment. METHODS: We selected two sites in each model of TB service in four provinces of China. In each site, 50 patients were selected from TB patient registries for a structured questionnaire survey, with a total of 293 patients recruited. All participants were newly registered uncomplicated TB cases without any major complications or resistance to first-line anti-TB drugs, and having successfully completed treatment. Diagnostic and treatment procedures were reviewed from medical charts of the surveyed patients to compare with national guidelines. RESULTS: Specialist sites had the highest patient expenditure, hospitalization rates and mostly used second-line anti-TB drugs, while the integrated model reported the opposite. The median health expenditure was USD 1,499 for the specialist sites and USD 306 for the integrated sites, with 83% and 15% patients respectively having unnecessary hospitalization. 74% of the specialist sites and 19% of the integrated sites used second-line anti-TB drugs. Mixed results were identified in the two dispensary sites. One site had median health expenditure of USD 138 with 12% of patients hospitalized, while the other had USD 912 and 65% respectively. CONCLUSION: The study observed prohibitive financial expenditure and a high level of deviation from national guidelines in all sites, which may be related to the profit-seeking behavior of public hospitals. The study supports the integrated model as the better policy option for future TB health reform in China.


title: Low Barrier Tele-Buprenorphine in the Time of COVID-19: A Case Report

text: BACKGROUND: To reduce the spread of coronavirus disease 2019 (COVID-19), many substance use disorder treatment programs have transitioned to telemedicine. Emergency regulatory changes allow buprenorphine initiation without an in-person visit. We describe the use of videoconferencing for buprenorphine initiation combined with street outreach to engage 2 patients experiencing homelessness with severe opioid use disorder (OUD). CASE PRESENTATION: Patient 1 was a 30-year-old man with severe OUD who had relapsed to injection heroin/fentanyl after incarceration. A community drop-in center outreach harm reduction specialist facilitated a videoconference with an addiction specialist at an OUD bridge clinic. The patient completed a community buprenorphine/naloxone initiation and self-titrated to his prior dose, 8/2 mg twice daily. One week later, he reconnected with the outreach team for a follow-up videoconference visit. Patient 2, a 36-year-old man with severe OUD, connected to the addiction specialist via a syringe service program harm reduction specialist. He had been trying to connect to a community buprenorphine/naloxone provider, but access was limited due to COVID-19, so he was using diverted buprenorphine/naloxone to reduce opioid use. He was restarted on his previous dose of 12/3 mg daily which was continued via phone follow-up 16 days later. CONCLUSIONS: COVID-19-related regulatory changes allow buprenorphine initiation via telemedicine. We describe 2 cases where telemedicine was combined with street outreach to connect patients experiencing homelessness with OUD to treatment. These cases highlight an important opportunity to provide access to life-saving OUD treatment for vulnerable patients in the setting of a pandemic that mandates reduced face-to-face clinical interactions.


title: A histomorphometric study on treated and untreated ceramic filled PEEK implants versus titanium implants: Preclinical in vivo study

text: OBJECTIVES: To investigate the osseo‐integrative behavior of untreated (UCFP) and sandblasted ceramic filled PEEK (SCFP) implants in comparison with titanium implants through measurement of bone implant contact (BIC) and bone density (BD). MATERIALS AND METHODS: Nine implants from each type were inserted into 9 dogs in which every experimental dog received the three different implants in the lower border of the mandible. The animals were euthanized after 3 months and extracting bone blocks containing implants followed by blocks preparation for histological examinations. RESULTS: BIC and BD were significantly higher in titanium and SCFP compared with UCFP group (p = .007) and (p = .012), respectively. Aluminum blasting increased the bone ingrowth and bone implant contact when compared to machined surfaces of untreated PEEK implants. CONCLUSION: In conclusion, sandblasting with 110 µm aluminum oxide particles can be proposed as a suitable surface treatment that enhances hydrophilicity of CFP. Further in vivo animal studies are still needed to confirm the findings of this study.


title: CRM1 Inhibitors for Antiviral Therapy

text: Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed. Overexpression of CRM1-mediated nuclear export is evident in several solid and hematological malignancies. Interestingly, CRM1-mediated nuclear export of viral components is crucial in various stages of the viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer and selected viruses. Leptomycin B (LMB) is the prototypical inhibitor of CRM1 potent against various cancer cell lines overexpressing CRM1 and in limiting viral infections at nanomolar concentrations in vitro. However, the irreversible shutdown of nuclear export results in high cytotoxicity and limited efficacy in vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can potentially be developed as broadly active antivirals, some of which are summarized in this review.


title: Metformin use amid coronavirus disease 2019 pandemic

text: There are a few aspects that we would like to add to complement the discussion in EL-Arabey and Abdalla [1]. Firstly, the authors suggested that the reduction of weight with the use of metformin, especially among obese patients, may have a protective effect on mortality from COVID-19. This article is protected by copyright. All rights reserved.


title: Chapter 21 New Emerging Viruses

text: Abstract Newly emerging viruses such as the Ebola virus, severe acute respiratory syndrome (SARS)-, Middle East respiratory syndrome (MERS)-coronavirus, and the avian influenza virus are serious threats to public health and have become a global concern. The swine flu pandemic which occurred in 2009 reminded us of the Spanish flu that killed over 40 million people. Newly emerging viruses could be either a novel previously undescribed virus or a variant of a previously known virus. Examples of the novel viruses include HIV, the Ebola virus, and SARS viruses. Variants of previously described viruses are also called “remerging viruses.” They are mutants of known viruses but cause new epidemics with considerable virulence. The influenza virus that caused the 2009 swine flu pandemic was a variant of an existing virus.


title: COMPLEMENT ACTIVATION IN PATIENTS WITH COVID-19: A NOVEL THERAPEUTIC TARGET

text: The pathophysiology of the severe complications of COVID-19 is still unclear. We report preliminary data providing evidence of complement activation in patients with COVID-19 with different degrees of respiratory failure.


title: Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients

text: Summary Background After the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea, prediction of pneumonia development and progression to respiratory failure was emphasized in control of MERS outbreak. Methods MERS-CoV infected patients who were managed in a tertiary care center during the 2015 Korean MERS outbreak were reviewed. To analyze predictive factors for pneumonia development and progression to respiratory failure, we evaluated clinical variables measured within three days from symptom onset. Results A total of 45 patients were included in the study: 13 patients (28.9%) did not develop pneumonia, 19 developed pneumonia without respiratory failure (42.2%), and 13 progressed to respiratory failures (28.9%). The identified predictive factors for pneumonia development included age ≥45 years, fever ≥37.5 °C, thrombocytopenia, lymphopenia, CRP ≥ 2 mg/dL, and a threshold cycle value of PCR less than 28.5. For respiratory failure, the indicators included male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, and CRP ≥ 4 mg/dL (all P < 0.05). With ≥ two predictive factors for pneumonia development, 100% of patients developed pneumonia. Patients lacking the predictive factors did not progress to respiratory failure. Conclusion For successful control of MERS outbreak, MERS-CoV infected patients with ≥ two predictive factors should be intensively managed from the initial presentation.


title: The potential role of TNFα in 2019 novel coronavirus pneumonia

text: The outbreak of 2019 novel coronavirus has spread rapidly in multiple countries. We report the first case of 2019-nCoV infection in a patient with Ankylosing Spondylitisthe (AS), who was a biological agent (anti-TNFα) user in Wenzhou, China, and describe the clinical course and management of the case.