title: Life-Threatening Psoas Hematoma due to Retroperitoneal Hemorrhage in a COVID-19 Patient on Enoxaparin Treated With Arterial Embolization: A Case Report

text: Respiratory failure is presumptively caused by microvascular thrombosis in some patients with coronavirus disease 2019 (COVID-19) requiring therapeutic anticoagulation. Anticoagulation treatment may cause life-threatening bleeding complications such as retroperitoneal hemorrhage. To the best of our knowledge, we report first case of a COVID-19 patient treated with therapeutic anticoagulation resulting in psoas hematoma due to lumbar artery bleeding. A 69-year-old patient presented with fever, malaise and progressive shortness of breath to our hospital. He was diagnosed with COVID-19 by RT-PCR. Due to an abnormal coagulation profile, the patient was started on enoxaparin. Over the course of hospitalization, the patient was found to have hypotension with worsening hemoglobin levels. Computed tomography scan of the abdomen and pelvis revealed a large psoas hematoma. Arteriogram revealed lumbar artery bleeding which was treated with embolization. Anticoagulation therapy, while indicated in COVID-19 patients, has its own challenges and guidelines describing dosages and indications in this disease are lacking. Rare bleeding complications such as psoas hematoma should be kept in mind in patients who become hemodynamically unstable, warranting prompt imaging for diagnosis and treatment with arterial embolization, thus eliminating need of surgical intervention.


title: Internationale Soziale Arbeit neu denken: Zur Verschärfung Globaler Ungleichheit durch COVID-19

text: Covid-19 hat sich über die ganze Welt ausbreitet und kann sie an den Rand eines ökonomischen und politischen Kollapses führen. Das Virus trifft zwar alle, doch mit Unterschieden. Die Krankheit wird zum einen die sozialen Probleme in den reichen Gesellschaften des Nordens verändern und auch vergrößern, doch insbesondere in den Ländern des Globalen Südens kann der Ausbruch in seinen ökonomischen und sozialen Folgen verheerend sein. Kann der Globale Norden noch eindämmende und die Folgen abfedernde Maßnahmen etablieren, so schlagen die Auswirkungen im Globalen Süden voll durch. In diesen Gesellschaften sind verheerende Folgen zu erwarten, die Armut, Elend, Hunger und Migrationsbewegungen intensivieren werden. Dadurch wird aber auch die Globale Ungleichheit zwischen den Nationen größer. In dieser Krise wäre Solidarität über nationale Grenzen hinweg gefragt; doch genau diese ist kaum erkennbar. Die Internationale Soziale Arbeit ist aufgefordert, ihre Ausrichtung neu zu definieren.


title: Case fatality of SARS in mainland China and associated risk factors

text: Objective To analyse the case fatality ratio (CFR) and its risk factors for severe acute respiratory syndrome (SARS) in mainland China by using a comprehensive dataset of all probable cases. Methods The data of all probable SARS cases were derived from the Infectious Disease Reporting System of the Center of Diseases Control and Hospital Information Systems, during the 2003 epidemic in mainland China. The definition of probable SARS case was consistent with the definition for clinically confirmed SARS issued by the Ministry of Health of the People’s Republic of China. We performed univariate and multivariate logistic regression analysis to determine the association of CFR with age, sex, residence location, occupation, the period of the epidemic and the duration from symptom onset to admission into hospital. Results The overall CFR was 6.4% among 5327 probable SARS cases in mainland China. Old age, being a patient during the early period of a local outbreak, and being from Tianjin led to a relatively higher CFR than young age, late stage of a local outbreak and cases from Beijing. Guangdong Province resulted in an even lower CFR compared with Beijing. Conclusions Because of their deteriorated health status and apparent complications, SARS patients aged >60 years had a much higher risk of dying than younger patients. At the early stage of local outbreaks, lack of experience in patient care and perhaps treatment also led to a relatively higher CFR. The Tianjin SARS outbreak happened mainly within a hospital, leading to a high impact of co‐morbidity. The relatively young age of the cases partly explains the low CFR in mainland China compared with other countries and areas affected by SARS.


title: Evaluation of reference genes for real-time quantitative PCR studies in Candida glabrata following azole treatment

text: BACKGROUND: The selection of stable and suitable reference genes for real-time quantitative PCR (RT-qPCR) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. The present study aimed to identify reference genes as internal controls for gene expression studies by RT-qPCR in azole-stimulated Candida glabrata. RESULTS: The expression stability of 16 reference genes under fluconazole stress was evaluated using fold change and standard deviation computations with the hkgFinder tool. Our data revealed that the mRNA expression levels of three ribosomal RNAs (RDN5.8, RDN18, and RDN25) remained stable in response to fluconazole, while PGK1, UBC7, and UBC13 mRNAs showed only approximately 2.9-, 3.0-, and 2.5-fold induction by azole, respectively. By contrast, mRNA levels of the other 10 reference genes (ACT1, EF1α, GAPDH, PPIA, RPL2A, RPL10, RPL13A, SDHA, TUB1, and UBC4) were dramatically increased in C. glabrata following antifungal treatment, exhibiting changes ranging from 4.5- to 32.7-fold. We also assessed the expression stability of these reference genes using the 2(-ΔΔCT) method and three other software packages. The stability rankings of the reference genes by geNorm and the 2(-ΔΔCT) method were identical to those by hkgFinder, whereas the stability rankings by BestKeeper and NormFinder were notably different. We then validated the suitability of six candidate reference genes (ACT1, PGK1, RDN5.8, RDN18, UBC7, and UBC13) as internal controls for ten target genes in this system using the comparative C(T) method. Our validation experiments passed for all six reference genes analyzed except RDN18, where the amplification efficiency of RDN18 was different from that of the ten target genes. Finally, we demonstrated that the relative quantification of target gene expression varied according to the endogenous control used, highlighting the importance of the choice of internal controls in such experiments. CONCLUSIONS: We recommend the use of RDN5.8, UBC13, and PGK1 alone or the combination of RDN5.8 plus UBC13 or PGK1 as reference genes for RT-qPCR analysis of gene expression in C. glabrata following azole treatment. In contrast, we show that ACT1 and other commonly used reference genes (GAPDH, PPIA, RPL13A, TUB1, etc.) were not validated as good internal controls in the current model.


title: Mathematical Analysis of Viral Replication Dynamics and Antiviral Treatment Strategies: From Basic Models to Age-Based Multi-Scale Modeling

text: Viral infectious diseases are a global health concern, as is evident by recent outbreaks of the middle east respiratory syndrome, Ebola virus disease, and re-emerging zika, dengue, and chikungunya fevers. Viral epidemics are a socio-economic burden that causes short- and long-term costs for disease diagnosis and treatment as well as a loss in productivity by absenteeism. These outbreaks and their socio-economic costs underline the necessity for a precise analysis of virus-host interactions, which would help to understand disease mechanisms and to develop therapeutic interventions. The combination of quantitative measurements and dynamic mathematical modeling has increased our understanding of the within-host infection dynamics and has led to important insights into viral pathogenesis, transmission, and disease progression. Furthermore, virus-host models helped to identify drug targets, to predict the treatment duration to achieve cure, and to reduce treatment costs. In this article, we review important achievements made by mathematical modeling of viral kinetics on the extracellular, intracellular, and multi-scale level for Human Immunodeficiency Virus, Hepatitis C Virus, Influenza A Virus, Ebola Virus, Dengue Virus, and Zika Virus. Herein, we focus on basic mathematical models on the population scale (so-called target cell-limited models), detailed models regarding the most important steps in the viral life cycle, and the combination of both. For this purpose, we review how mathematical modeling of viral dynamics helped to understand the virus-host interactions and disease progression or clearance. Additionally, we review different types and effects of therapeutic strategies and how mathematical modeling has been used to predict new treatment regimens.


title: Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign

text: BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA. METHODOLOGY/PRINCIPAL FINDINGS: To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007. CONCLUSION/SIGNIFICANCE: Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs.


title: Genomic medicine and developing countries: creating a room of their own

text: The notion that developing countries must wait for the developed world to make advances in science and technology that they later import at great cost is being challenged. We have previously argued that developing countries can harness human genetic variation to benefit their populations and economies. Based on our empirical studies of large-scale population genotyping projects in Mexico, India and Thailand, we describe how these resources are being adopted to improve public health and create knowledge-based economies. A significant additional benefit is building the capacity for scientific research and internalizing advances in technology, whatever their source.


title: Post-translational glycosylation of coronavirus glycoprotein E1: inhibition by monensin.

text: The intracellular sites of biosynthesis of the structural proteins of murine hepatitis virus A59 have been analyzed using cell fractionation techniques. The nucleocapsid protein N is synthesized on free polysomes, whereas the envelope glycoproteins E1 and E2 are translated on the rough endoplasmic reticulum (RER). Glycoprotein E2 present in the RER contains N-glycosidically linked oligosaccharides of the mannose-rich type, supporting the concept that glycosylation of this protein is initiated at the co-translational level. In contrast, O-glycosylation of E1 occurs after transfer of the protein to smooth intracellular membranes. Monensin does not interfere with virus budding from the membranes of the endoplasmic reticulum, but it inhibits virus release and fusion of infected cells. The oligosaccharide side chains of E2 obtained under these conditions are resistant to endoglycosidase H and lack fucose suggesting that transport of this glycoprotein is inhibited between the trans Golgi cisternae and the cell surface. Glycoprotein E1 synthesized in the presence of monensin is completely carbohydrate-free. This observation suggests that the intracellular transport of this glycoprotein is also blocked by monensin.


title: Purkinje cell neuroaxonal dystrophy similar to nervous mutant mice phenotype in two sibling kittens

text: Three 4-month-old kittens from the same litter were presented, two of which were exhibiting cerebellar signs. Euthanasia was requested. No cerebellum atrophy was disclosed on necropsy. General cerebellar anatomy was normal, including the thickness of the cortical layers, myelination, and neurons of the deep cerebellar nuclei. In the ataxic cat vermis, Purkinje cells were lacking along broad parasagittal bands symmetrically disposed relative to the midline. Many Purkinje cells were also lacking in the hemispheres. The nodulus and the flocculus were normal. Surviving Purkinje cells had frequent main dendrite swellings visible with anti-calbindin and anti-microtubule associated protein. In affected regions, calbindin and phosphorylated neurofilaments immunesera stained numerous axonal torpedoes located in the granular layer and the folial white matter. They were also present in processes of the deep cerebellar nuclei and lateral vestibular nucleus. Loss of synaptic endings onto the neurons of these nuclei was evident. Hypertrophied Purkinje cell recurrent axons and enhanced retrograde synaptic endings were present in the granular layer. Bergmann glia was strongly labeled by anti-GFAP, but no abnormal supplementary fibers were seen. None of these alterations were present in the normal sister. However, abnormal vacuolation of the Purkinje cell main dendrites was evident in all three cats, but not in six unrelated control cats that were 3–6 months old. The inferior olive and pontine nuclei were also normal. The two ataxic cats had a primary Purkinje cell degeneration that shared many common features with the abnormal Purkinje cells of the nervous mutant mouse.


title: Comparison of drug abuse in Germany and China

text: Drug abuse has a long, but also different history in Germany and China. The Opium War largely influenced the history of China in 19th century; however, China was once recognized as a drug-free nation for 3 decades from the 1950s to the 1980s. Drug abuse has spread quickly since re-emerging as a national problem in China in the late 1980s. The number of registered drug abusers increased from 70 000 in 1990 to more than 1 million by the end of 2005. In past decades, illicit drug trafficking and production have swept most provinces in China, and drug abuse has caused many problems for both abusers and the community. One major drug-related problem is the spread of HIV, which has caused major social and economic damage in China. Germany, the largest developed European country, also faces the drug and addiction problem. Germany has about 150 000 heroin addicts, for whom HIV/AIDS has become a serious threat since the mid 1980s. To control the drug problem, the German Government adopted the “Action Plan on Drugs and Addiction” in 2003; the China Central Government approved a similar regulation in the antidrug campaign in 2005. Germany has experience in reducing drug-related harm. The methadone maintenance treatment (MMT) program has run for more than 20 years and the public has become more tolerant of addicts. In 2003, China began the MMT program for controlling the spread of HIV/AIDS. It is necessary for China to learn from developed countries to acquire success in its antidrug campaign. In this review, we will go over the differences and similarities in drug abuse between Germany and China. The differences are related to history, population and economics, drug policy context, drug laws, HIV/hepatitis C virus infection, the MMT program and so on. These 2 nations have drug abuse problems with different histories and currently use different approaches to handle illicit drug marketing and use. The legal penalties for illicit drug offences reflect the social differences of these 2 nations with respect to the seriousness of particular types of crimes. The characteristics of the MMT program may also influence patterns of drug abuse in these 2 nations and China should improve the MMT program based on the successful model in Europe, the USA, and Australia. We recommend more dialogue and collaboration between Germany and China.


title: Fatal Superimposed Bacterial Sepsis in a Healthy Coronavirus (COVID-19) Patient

text: Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the newly discovered coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The novel coronavirus first emerged in Wuhan, China, in December 2019 and has led to a global pandemic. The virus mainly spreads through respiratory droplets from an infected person, but environmental contamination can also act as a source of infection, making social distancing an important key in containing the spread of infection. Those with underlying health conditions are more susceptible to complications such as acute respiratory distress syndrome, which can be fatal. However, healthy individuals experience a mild flu-like illness or may be asymptomatic, recuperating from the infection even without any particular intervention. We present a case of a healthy COVID positive individual, with no underlying comorbidities, who rapidly deteriorated overnight on readmission to the hospital after initial discharge and succumbed to this disease due to a superimposed bacterial infection with COVID pneumonia. This case report highlights the importance of educating COVID-19 positive patients about the precautions, as well as signs and symptoms of a superimposed bacterial infection, when their plan of care is in a home setting. It also emphasizes the potential role of checking procalcitonin levels as a part of routine laboratory investigation at initial presentation in all suspected as well as confirmed COVID-19 cases to rule out an on-going bacterial infection that can prove fatal in the course of the disease.


title: Recombinant Plant Engineering for Immunotherapeutic Production

text: PURPOSE OF REVIEW: The requirement for large quantities of therapeutic proteins has fueled a great interest in the production of recombinant proteins in plant bioreactors. The vaccines and bio-therapeutic protein production in plants hold the promise of significantly lowering the cost of manufacturing life-saving drugs. This review will reflect the current status and challenges that the molecular farming platform faces becoming a strategic solution for the development of low-cost bio-therapeutics for developing countries. RECENT FINDINGS: Different plant parts have been successfully identified as suitable expression systems for the commercial production of therapeutic proteins for some human and animal diseases ranging from common cold to AIDS. The processed therapeutics from such sources are devoid of any toxic components. The large-scale cultivation of these transgenic plants would be possible anywhere in the world including developing countries, which lack sophisticated drug manufacturing units. A couple of such commercially generated products have already hit the market with success. Newer methods using suitable plant viruses and recombinant gene expression systems have already been devised for producing therapeutic proteins and peptides. SUMMARY: Plants are promising bio-factories for therapeutic protein production because of their several advantages over the other expression systems especially the advanced mechanisms for protein synthesis and post-translational modification which are very much similar to animal cells. Plant biotechnologists are much attracted to the bio-farming because of its flexibility, scalability, low manufacturing cost, as well as the lack of risk of toxic or pathogenic contamination. A number of projects on bio-farming are designed and are at various developmental stages but have not yet become available to the pharmaceutical industry. Therefore, we need further advancement in the optimization of lab protocols for up-scaling the production of such therapeutics at commercial level with a promise to offer their best clinical use.


title: Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda

text: Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2–54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.


title: Interaction Between Virus-Like Particles (VLPs) and Pattern Recognition Receptors (PRRs) From Dendritic Cells (DCs): Toward Better Engineering of VLPs

text: Virus-like particles (VLPs) have been shown to be strong activators of dendritic cells (DCs). DCs are the most potent antigen presenting cells (APCs) and their activation prompts the priming of immunity mediators based on B and T cells. The first step for the activation of DCs is the binding of VLPs to pattern recognition receptors (PRRs) on the surface of DCs, followed by VLP internalization. Like wild-type viruses, VLPs use specific PRRs from the DC; however, these recognition interactions between VLPs and PRRs from DCs have not been thoroughly reviewed. In this review, we focused on the interaction between proteins that form VLPs and PRRs from DCs. Several proteins that form VLP contain glycosylations that allow the direct interaction with PRRs sensing carbohydrates, prompting DC maturation and leading to the development of strong adaptive immune responses. We also discussed how the knowledge of the molecular interaction between VLPs and PRRs from DCs can lead to the smart design of VLPs, whether based on the fusion of foreign epitopes or their chemical conjugation, as well as other modifications that have been shown to induce a stronger adaptive immune response and protection against infectious pathogens of importance in human and veterinary medicine. Finally, we address the use of VLPs as tools against cancer and allergic diseases.


title: Emergency Department Response to SARS, Taiwan

text: How emergency departments of different levels and types cope with a large-scale contagious infectious disease is unclear. We retrospectively analyzed the response of 100 emergency departments regarding use of personal protective equipment (PPE) and implementation of infection control measures (ICMs) during the severe acute respiratory syndrome outbreak in Taiwan. Emergency department workers in large hospitals were more severely affected by the epidemic. Large hospitals or public hospitals were more likely to use respirators. Small hospitals implemented more restrictive ICMs. Most emergency departments provided PPE (80%) and implemented ICMs (66%) at late stages of the outbreak. Instructions to use PPE or ICMs more frequently originated by emergency department administrators. The difficulty of implementing ICMs was significantly negatively correlated with their effectiveness. Because ability to prepare for and respond to emerging infectious diseases varies among hospitals, grouping infectious patients in a centralized location in an early stage of infection may reduce the extent of epidemics.


title: Biological and Clinical Basis for Molecular Studies of Interferons

text: The cytokine family of interferons (IFNs) has multiple functions, including antiviral, antitumor, and immunomodulatory effects and regulation of cell differentiation. The multiple functions of the IFN system are thought to be an innate defense against microbes and foreign substances. The IFN system consists first of cells that produce IFNs in response to viral infection or other foreign stimuli and second of cells that establish the antiviral state in response to IFNs. This process of innate immunity involves multiple signaling mechanisms and activation of various host genes. Viruses have evolved to develop mechanisms that circumvent this system. IFNs have also been used clinically in the treatment of viral diseases. Improved treatments will be possible with better understanding of the IFN system and its interactions with viral factors. In addition, IFNs have direct and indirect effects on tumor cell proliferation, effector leukocytes and on apoptosis and have been used in the treatment of some cancers. Improved knowledge of how IFNs affect tumors and the mechanisms that lead to a lack of response to IFNs would help the development of better IFN treatments for malignancies.


title: American Geriatrics Society Policy Brief: COVID‐19 and Nursing Homes

text: This policy brief sets forth the American Geriatrics Society's (AGS's) recommendations to guide federal, state, and local governments when making decisions about care for patients with coronavirus disease 2019 (COVID‐19) in nursing homes (NHs) and other long‐term care facilities (LTCFs). The AGS continues to review guidance set forth in peer‐reviewed articles and editorials, as well as ongoing and updated guidance from the Centers for Medicare and Medicaid Services, the Centers for Disease Control and Prevention, and other key agencies. This brief is based on the situation and any federal guidance/actions as of April 4, 2020. It is focused on NHs and other LTCFs, given their essential role in addressing the COVID‐19 pandemic. J Am Geriatr Soc 68:908–911, 2020


The Edinburgh microbiology archive


title: Public Interest in Preventive Measures of Coronavirus Disease 2019 Associated With Timely Issuance of Statewide Stay-at-Home Orders

text: INTRODUCTION: One method of monitoring public preparedness is through measuring public interest in preventive measures. The objective of this study was to analyze public interest in the coronavirus disease 2019 (COVID-19) preventive measures and to identify variables associated with timely stay-at-home (SAH) orders issued by governors. METHODS: State-level search volume was collected from Google Trends. Average preventive measure interest was calculated for the query terms “hand sanitizer,” “hand washing,” “social distancing,” and “COVID testing.” We then calculated the delay in statewide SAH orders from March 1, 2020, to the date of issuance and by-state presidential voting percentage. Bivariate correlations were computed to assess the relationship between interest in preventive measures and SAH order delay. RESULTS: The correlation between average preventive measure interest and length of time before the SAH order was placed was −0.47. Average preventive measure interest was also inversely related to voting for a Republican presidential nominee in the 2016 election (R = −0.75), the latter of which was positively associated with longer delays in SAH orders (R = 0.48). CONCLUSIONS: States with greater public interest in COVID-19 preventive measures were inversely related to governor issuance of timely SAH orders. Increasing public interest in preventive measures may slow the spread of the virus that causes COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by improving preparedness.


title: Evaluation on the Efficacy and Immunogenicity of Recombinant DNA Plasmids Expressing Spike Genes from Porcine Transmissible Gastroenteritis Virus and Porcine Epidemic Diarrhea Virus

text: Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PDEV) can cause severe diarrhea in pigs. Development of effective vaccines against TGEV and PEDV is one of important prevention measures. The spike (S) protein is the surface glycoprotein of TGEV and PEDV, which can induce specific neutralization antibodies and is a candidate antigen for vaccination attempts. In this study, the open reading frames of the TGEV S1 protein and in addition of the S or S1 proteins of PEDV were inserted into the eukaryotic expression vector, pIRES, resulting in recombinant plasmids, pIRES-(TGEV-S1-PEDV-S1) and pIRES-(TGEV-S1-PEDV-S). Subsequently, 6–8 weeks old Kunming mice were inoculated with both DNA plasmids. Lymphocyte proliferation assay, virus neutralization assay, IFN-γ assay and CTL activity assay were performed. TGEV/PEDV specific antibody responses as well as kinetic changes of T lymphocyte subgroups of the immunized mice were analyzed. The results showed that the recombinant DNA plasmids increased the proliferation of T lymphocytes and the number of CD4+ and CD8+ T lymphocyte subgroups. In addition, the DNA vaccines induced a high level of IFN-γ in the immunized mice. The specific CTL activity in the pIRES-(TGEV-S1-PEDV-S) group became significant at 42 days post-immunization. At 35 days post-immunization, the recombinant DNA plasmids bearing full-length S genes of TGEV and PEDV stimulated higher levels of specific antibodies and neutralizing antibodies in immunized mice.


title: Obesity and COVID-19: immune and metabolic derangement as a possible link to adverse clinical outcomes

text: Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as “cytokine storm,” while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.


title: Treatable traits and therapeutic targets: Goals for systems biology in infectious disease

text: Abstract Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing. A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be static – serial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients.


title: COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review

text: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presently become a rapidly spreading and devastating global pandemic. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory compromise such as that induced by SARS-CoV-2. While still little is known on the true efficacy of ECMO in this setting, the natural resemblance of seasonal influenza’s characteristics with respect to acute onset, initial symptoms, and some complications prompt to ECMO implantation in most severe, pulmonary decompensated patients. The present review summarizes the evidence on ECMO management of severe ARDS in light of recent COVID-19 pandemic, at the same time focusing on differences and similarities between SARS-CoV-2 and ECMO in terms of hematological and inflammatory interplay when these two settings merge.


title: Experimental infection in calves with a specific subtype of verocytotoxin-producing Escherichia coli O157:H7 of bovine origin

text: BACKGROUND: In Sweden, a particular subtype of verocytotoxin-producing Escherichia coli (VTEC) O157:H7, originally defined as being of phage type 4, and carrying two vtx(2 )genes, has been found to cause the majority of reported human infections during the past 15 years, including both sporadic cases and outbreaks. One plausible explanation for this could be that this particular subtype is better adapted to colonise cattle, and thereby may be excreted in greater concentrations and for longer periods than other VTEC O157:H7 subtypes. METHODS: In an experimental study, 4 calves were inoculated with 10(9 )colony forming units (cfu) of strain CCUG 53931, representative of the subtype VTEC O157:H7 (PT4;vtx(2);vtx(2c)). Two un-inoculated calves were co-housed with the inoculated calves. Initially, the VTEC O157:H7 strain had been isolated from a dairy herd with naturally occurring infection and the farm had previously also been linked to human infection with the same strain. Faecal samples were collected over up to a 2-month period and analysed for VTEC O157 by immuno-magnetic separation (IMS), and IMS positive samples were further analysed by direct plating to elucidate the shedding pattern. Samples were also collected from the pharynx. RESULTS: All inoculated calves proved culture-positive in faeces within 24 hours after inoculation and the un-inoculated calves similarly on days 1 and 3 post-inoculation. One calf was persistently culture-positive for 43 days; in the remainder, the VTEC O157:H7 count in faeces decreased over the first 2 weeks. All pharyngeal samples were culture-negative for VTEC O157:H7. CONCLUSION: This study contributes with information concerning the dynamics of a specific subtype of VTEC O157:H7 colonisation in dairy calves. This subtype, VTEC O157:H7 (PT4;vtx(2;)vtx(2c)), is frequently isolated from Swedish cattle and has also been found to cause the majority of reported human infections in Sweden during the past 15 years. In most calves, inoculated with a representative strain of this specific subtype, the numbers of shed bacteria declined over the first two weeks. One calf could possibly be classified as a high-shedder, excreting high levels of the bacterium for a prolonged period.


title: MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles

text: Hepatitis C virus (HCV) has infected around 160 million individuals. Current therapies have limited efficacy and are fraught with side effects. To identify cellular HCV dependency factors, possible therapeutic targets, we manipulated signaling cascades with pathway-specific inhibitors. Using this approach we identified the MAPK/ERK regulated, cytosolic, calcium-dependent, group IVA phospholipase A2 (PLA2G4A) as a novel HCV dependency factor. Inhibition of PLA2G4A activity reduced core protein abundance at lipid droplets, core envelopment and secretion of particles. Moreover, released particles displayed aberrant protein composition and were 100-fold less infectious. Exogenous addition of arachidonic acid, the cleavage product of PLA2G4A-catalyzed lipolysis, but not other related poly-unsaturated fatty acids restored infectivity. Strikingly, production of infectious Dengue virus, a relative of HCV, was also dependent on PLA2G4A. These results highlight previously unrecognized parallels in the assembly pathways of these human pathogens, and define PLA2G4A-dependent lipolysis as crucial prerequisite for production of highly infectious viral progeny.


title: B-cell restriction – an alternative piece to the puzzle

text: Effective vaccination is based on three critical aspects of the B-cell response towards infectious agents: (i) that B-cells can generate specific antibodies towards a vast molecular diversity of antigens; proteins, sugars, DNA and lipids. There seems to be no limit to the ability to raise antibodies to everything. (ii) once stimulated, B-cells can perfect their antibodies through affinity maturation to complement every nook and cranny of the epitope and (iii) that the pathogen remains genetically stable and does not change to any great extent. Thus, antibodies produced against the vaccine and subsequent boosts recognize the viral virulent field isolates in future encounters and effectively knock them out. However, some vaccine targets, such as flu virus and HIV, are extremely genetically dynamic. The rapid genetic drift of these viruses renders them moving targets which assist in their ability to evade immune surveillance. Here we postulate that in the case of hyper-variable pathogens the B-cell response actually might be “too good”. We propose that restricting B-cell activities may prove effective in counteracting the genetic diversity of variant viruses such as flu and HIV. We suggest two levels of “B-cell restriction”: (i) to focus the B-cell response exclusively towards neutralizing epitopes by creating epitope-based immunogens; (ii) to restrict affinity maturation of B-cells to prevent the production of overly optimized exquisitely specific antibodies. Together, these “B-cell restrictions” provide a new modality for vaccine design.


title: Taming COVID-19 by Regulation: An Opportunity for Self-Reflection

text: The COVID-19 outbreak is not the first nor last series of recent real or potential catastrophes - be they natural disasters, terrorist attacks or pandemics - that have taken by surprise governments, globalised firms and the citizenry. 1Yet, due to its near-unprecedented impact on the highly interconnected but vulnerable systems that define the modern world, this pandemic has been testing our ability to govern risk more than any other crisis before. The last time the world responded to a global emerging disease epidemic of the scale of the current novel coronavirus without having access to vaccines was the 1918-1919 H1N1 influenza pandemic. 2Ironically, the measures mobilised today to counter COVID-19 - the so-called “non-pharmaceutical interventions” 3- are essentially the same as those deployed a century ago, and that despite significant social, technological as well as governance differences between 1918 and today. 4


title: The association of lung ultrasound images with COVID‐19 infection in an emergency room cohort

text: Lung ultrasound could facilitate the triage of patients with suspected COVID‐19 infection admitted to the emergency room. We developed a predictive model for COVID‐19 diagnosis based on lung ultrasound and clinical features. We used ultrasound to image the lung bilaterally at two anterior sites, one and two hands below each clavicle, and a posterolateral site that was the posterior transverse continuation from the lower anterior site. We studied 100 patients, 31 of whom had a COVID‐19 positive reverse transcriptase polymerase chain reaction. A positive test was independently associated with: quick sequential organ failure assessment score ≥ 1; ≥ 3 B‐lines at the upper site; consolidation and thickened pleura at the lower site; and thickened pleura line at the posterolateral site. The model discrimination was an area (95%CI) under the receiver operating characteristic curve of 0.82 (0.75‐0.90). The characteristics (95%CI) of the model’s diagnostic threshold, applied to the population from which it was derived, were: sensitivity, 97% (83–100%); specificity, 62% (50–74%); positive predictive value, 54% (41–98%); and negative predictive value, 98% (88–99%). This model may facilitate triage of patients with suspected COVID‐19 infection admitted to the emergency room.


title: Lung Ultrasound Can Influence the Clinical Treatment of Pregnant Women With COVID‐19

text: Lung ultrasound (LUS) is an effective tool to detect and monitor patients infected with 2019 coronavirus disease (COVID‐19). The use of LUS on pregnant women is an emerging trend, considering its effectiveness during the outbreak. Eight pregnant women with a diagnosis of COVID‐19 confirmed by nasal/throat real‐time reverse transcription polymerase chain reaction testing who underwent point‐of‐care LUS examinations after routine obstetric ultrasound are described. A routinely performed LUS examination revealed serious lung involvement in 7 cases: 2 were initially asymptomatic; 3 have chest computed tomography; 1 had initial negative real‐time reverse transcription polymerase chain reaction results; and 1 had initial negative computed tomographic findings. Treatment for COVID‐19 was either commenced or changed in 87.5% of the patients (n = 7 of 8) on LUS findings. Among patients with abnormal LUS findings, treatment was commenced in 5 patients (71.5%) and changed in 2 patients (28.5%). One normal and 7 abnormal LUS cases indicate the impact of routine LUS on the clinical outcome and treatment of pregnant women.


title: Microbial diversity involved in the etiology of a bovine respiratory disease outbreak in a dairy calf rearing unit

text: The etiological agents involved in a bovine respiratory disease (BRD) outbreak were investigated in a dairy heifer calf rearing unit from southern Brazil. A battery of PCR assays was performed to detect the most common viruses and bacteria associated with BRD, such as bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine alphaherpesvirus 1 (BoHV-1), bovine coronavirus (BCoV), bovine parainfluenza virus 3 (BPIV-3), Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. Bronchoalveolar lavage fluid (BALF) samples were taken from 21 heifer calves (symptomatic n = 15; asymptomatic n = 6) that, during the occurrence of the BDR outbreak, were aged between 6 and 90 days. At least one microorganism was detected in 85.7% (18/21) of the BALF samples. Mixed infections were more frequent (72.2%) than single infections (27.7%). The interactions between viruses and bacteria were the most common in coinfections (55.5%). The frequencies of BRD agents were 38.1% for BRSV, 28.6% for BVDV, 33.3% for BCoV, 42.85% for P. multocida, 33.3% for M. bovis, and 19% for H. somni. BoHV-1, BPIV-3, and M. haemolytica were not identified in any of the 21 BALF samples. Considering that BALF and not nasal swabs were analyzed, these results demonstrate the etiological multiplicity that may be involved in BRD outbreaks in dairy calves.


title: The ATP synthase subunit β (ATP5B) is an entry factor for the hepatitis E virus

text: Hepatitis E occurs sporadically and as outbreaks due to contamination of drinking water. The causative agent, hepatitis E virus (HEV) is a hepatotropic non-enveloped RNA virus, which grows poorly in vitro. Consequently, many aspects of HEV biology are poorly characterized, including its cellular receptor and entry mechanism(s). Previous studies from our laboratory have shown that heparan sulfate proteoglycans (HSPGs) act as attachment factors for the virus. In the absence of purified high titer infectious virus, we have used hepatitis E virus-like particles (HEV-LPs) expressed and purified from E. coli to identify HEV entry factor(s) on liver cells in culture. Using a pull down and mass spectrometric approach, we identified the ATP synthase subunit β (ATP5B) to bind the HEV capsid protein. Its role in the entry of HEV was then validated using antibody and siRNA mediated approaches, and infectious HEV from the stools of a hepatitis E patient. Though ATP synthase is largely a mitochondrial protein, the cell surface expressed form of ATP5B is implicated in other viral infections.


title: Spatial pattern of genetic diversity and selection in the MHC class II DRB of three Neotropical bat species

text: BACKGROUND: Although bats are natural reservoirs of many pathogens, few studies have been conducted on the genetic variation and detection of selection in major histocompatibility complex (MHC) genes. These genes are critical for resistance and susceptibility to diseases, and host–pathogen interactions are major determinants of their extensive polymorphism. Here we examined spatial patterns of diversity of the expressed MHC class II DRB gene of three sympatric Neotropical bats, Carollia perspicillata and Desmodus rotundus (Phyllostomidae), and Molossus molossus (Molossidae), all of which use the same environments (e.g., forests, edge habitats, urban areas). Comparison with neutral marker (mtDNA D-loop) diversity was performed at the same time. RESULTS: Twenty-three DRB alleles were identified in 19 C. perspicillata, 30 alleles in 35 D. rotundus and 20 alleles in 28 M. molossus. The occurrence of multiple DRB loci was found for the two Phyllostomidae species. The DRB polymorphism was high in all sampling sites and different signatures of positive selection were detected depending on the environment. The patterns of DRB diversity were similar to those of neutral markers for C. perspicillata and M. molossus. In contrast, these patterns were different for D. rotundus for which a geographical structure was highlighted. A heterozygote advantage was also identified for this species. No recombination or gene conversion event was found and phylogenetic relationships showed a trans-species mode of evolution in the Phyllostomids. CONCLUSIONS: This study of MHC diversity demonstrated the strength of the environment and contrasting pathogen pressures in shaping DRB diversity. Differences between positively selected sites identified in bat species highlighted the potential role of gut microbiota in shaping immune responses. Furthermore, multiple geographic origins and/or population admixtures observed in C. perspicillata and M. molossus populations acted as an additional force in shaping DRB diversity. In contrast, DRB diversity of D. rotundus was shaped by environment rather than demographic history. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-016-0802-1) contains supplementary material, which is available to authorized users.


title: Genomic Characterization of a Circovirus Associated with Fatal Hemorrhagic Enteritis in Dog, Italy

text: Dog circovirus (DogCV) was identified in an outbreak of enteritis in pups in Italy. The disease was observed in 6 young dachshunds pups of a litter from a breeding kennel and caused the death of 2 dogs. Upon full-genome analysis, the virus detected in one of the dead pups (strain Bari/411–13) was closely related to DogCVs that have been recently isolated in the USA. The present study, if corroborated by further reports, could represent a useful contribution to the knowledge of the pathogenic potential of DogCV and its association with enteritis in dogs.


title: Fecal Viral Concentration and Diarrhea in Norovirus Gastroenteritis

text: Fecal viral concentrations of 40 patients infected with norovirus genogroup GII.4 correlated with diarrhea duration and frequency of vomiting. Higher viral concentration and older age were independently associated with prolonged diarrhea (>4 days). These findings provide information on the pathogenesis and transmission of norovirus infections.


title: How many jobs can be done at home?()

text: Evaluating the economic impact of “social distancing” measures taken to arrest the spread of COVID-19 raises a fundamental question about the modern economy: how many jobs can be performed at home? We classify the feasibility of working at home for all occupations and merge this classification with occupational employment counts. We find that 37% of jobs in the United States can be performed entirely at home, with significant variation across cities and industries. These jobs typically pay more than jobs that cannot be done at home and account for 46% of all US wages. Applying our occupational classification to 85 other countries reveals that lower-income economies have a lower share of jobs that can be done at home.


title: Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic—an international perspective

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced ‘lockdowns’ are the new ‘norm’ as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.


title: An Experimental Model for Dilated Cardiomyopathy after Rabbit Coronavirus Infection

text: A rabbit model for coronavirus-induced dilated cardiomyopathy is described. Acute rabbit coronavirus infection results in virus-induced myocarditis and congestive heart failure. Of the survivors of rabbit coronavirus infection, 41% had increased heart weight and heart weight-to-body weight ratios, biventricular dilation, myocyte hypertrophy, myocardial fibrosis, and myocarditis consistent with the development of dilated cardiomyopathy. These changes were also seen in the remaining 59% of the survivors, except that the degree of myocyte hypertrophy was reduced and only right ventricular dilation was present. In most survivors, myocarditis was usually mild (1–5 foci/transverse section), but in some cases it was severe (>20 foci/transverse section). Interstitial and replacement fibrosis was more pronounced in the papillary muscles. These data suggest that rabbit coronavirus infection may progress to dilated cardiomyopathy.


title: Cytologic and molecular correlates of SARS-CoV-2 infection of the nasopharynx

text: Infection by SARS-CoV-2 commonly begins in the nasopharynx, and the cytologic and molecular correlates are not characterized. Fifty-eight cytologic preps (20 oral and 38 from the nasopharynx) were obtained from ten patients and analyzed in a blinded fashion for SARS-CoV-2 spike and envelope protein by immunohistochemistry and viral RNA by in situ hybridization. qRTPCR identified three positive cases and seven controls; the three cases reported mild symptoms that resolved in 2–3 days. Blinded analyses confirmed the presence of the SARS-CoV-2 spike and envelope proteins and viral RNA in the three cases and viral absence in the seven controls. A signal for the positive cases was evident in each nasopharyngeal and none of the oral samples. Viral RNA/proteins localized exclusively to glandular cells and was present in high copy number. Blinded analysis of the cytology documented that the glandular cells infected by SARS-CoV-2 showed marked degeneration with ciliocytophthoria; viral inclusions were not evident. Co-expression analysis showed viral infected cells had increased apoptosis, marked by strong expression of activated caspase 3. Weekly serial testing of two of the cases showed persistence of productive viral infection for up to 2 weeks after symptom onset. It is concluded that the target cell of SARS-CoV-2 in the head and neck region is the glandular cell of the nasal passages, that viral infection is lytic and associated with high copy number that facilitates viral spread. The method outlines a simple, rapid test for productive SARS-CoV-2 based on immunohistochemistry or in situ hybridization of the glandular cells from the nasopharynx.


title: Chapter 15 Proteomics of viruses

text: Publisher Summary Proteomics is a promising approach for the study of viruses allowing a better understanding of disease processes and the development of new biomarkers for diagnosis and early detection of disease, thus accelerating drug development. Viral proteomics has included the analysis of viral particles to determine all proteins that compose the infectious virus, the examination of cellular proteins associated with a single viral protein in the hopes of determining all the functions of that viral protein, or the determination of cellular proteins induced or altered during a particular disease state. Viral particles of human cytomegalovirus (HCMV) and Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) have been recently examined. During the herpesviral replicative cycle, different viral particles are formed. For HCMV, this includes mature, infectious virions, noninfectious enveloped particles, and dense bodies. A proteome database of B-lymphoblastoid cell lines (LCLs), before and after transformation, has been developed to identify the cellular mechanisms of virus-induced immortalization. 2DE is used to first separate proteins based on their relative charge (pI) and then based on their molecular weight. Proteomic analysis has provided a unique tool for the identification of diagnostic biomarkers, evaluation of disease progression, and drug development. It is also an important approach for clinical diagnostics.


title: Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

text: Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-l-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-l-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and anti-inflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.


title: COVID‐19 and Older Adults: What We Know

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a novel virus that causes COVID‐19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE‐2 receptor, the very receptor that the SARS‐CoV‐2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID‐19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID‐19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926–929, 2020


title: Using the prone position could help to combat the development of fast hypoxia in some patients with COVID‐19

text: The world is facing an explosive COVID‐19 pandemic. Some cases rapidly develop deteriorating lung function, which causes deep hypoxaemia and requires urgent treatment. Many centres have started treating patients in the prone position, and oxygenation has improved considerably in some cases. Questions have been raised regarding the mechanisms behind this. The mini review provides some insights into the role of supine and prone body positions and summarises the latest understanding of the responsible mechanisms. The scope for discussion is outside the neonatal period and entirely based on experimental and clinical experiences related to adults. The human respiratory system is a complex interplay of many different variables. Therefore, this mini review has prioritised previous and ongoing research to find explanations based on three scientific areas: gravity, lung structure and fractal geometry and vascular regulation. It concludes that gravity is one of the variables responsible for ventilation/perfusion matching but in concert with lung structure and fractal geometry, ventilation and regulation of lung vascular tone. Since ventilation distribution does not change between supine and prone positions, the higher expression of nitric oxide in dorsal lung vessels than in ventral vessels is likely to be the most important mechanism behind enhanced oxygenation in the prone position.


title: Beyond cells – The virome in the human holobiont

text: Viromics, or viral metagenomics, is a relatively new and burgeoning field of research that studies the complete collection of viruses forming part of the microbiota in any given niche. It has strong foundations rooted in over a century of discoveries in the field of virology and recent advances in molecular biology and sequencing technologies. Historically, most studies have deconstructed the concept of viruses into a simplified perception of viral agents as mere pathogens, which demerits the scope of large-scale viromic analyses. Viruses are, in fact, much more than regular parasites. They are by far the most dynamic and abundant entity and the greatest killers on the planet, as well as the most effective geo-transforming genetic engineers and resource recyclers, acting on all life strata in any habitat. Yet, most of this uncanny viral world remains vastly unexplored to date, greatly hindered by the bewildering complexity inherent to such studies and the methodological and conceptual limitations. Viromic studies are just starting to address some of these issues but they still lag behind microbial metagenomics. In recent years, however, higher-throughput analysis and resequencing have rekindled interest in a field that is just starting to show its true potential. In this review, we take a look at the scientific and technological developments that led to the advent of viral and bacterial metagenomics with a particular, but not exclusive, focus on human viromics from an ecological perspective. We also address some of the most relevant challenges that current viral studies face and ponder on the future directions of the field.


title: Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications

text: The renin–angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type‐1 receptor (AT(1)) and, together with ACE, these components represent the ‘classical’ axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang‐(1–7). Conceptually, ACE2, Ang‐(1–7), and its putative receptor, the mas receptor represent an ‘alternative’ axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease.


title: Efficacy and safety of Reduqing granules in the treatment of common cold with wind-heat syndrome: a randomized, double-blind, double-dummy, positive-controlled trial

text: Abstract Objective To assess the efficacy and safety of Reduqing granules in patients with common cold with wind-heat syndrome (CCWHS). Methods A randomized, double-blind, double-dummy, parallel, positive-controlled trial included 72 CCWHS patients was performed. The participants were randomly assigned to two groups, Reduqing (RDQ) group and Lianhuaqingwen (LHQW) group, in a 1:1 ratio. Patients in RDQ group received Reduqing granules and dummy Lianhuaqingwen capsules three times a day and patients in LHQW group received Lianhuaqingwen capsules and dummy Reduqing granules three times daily. The duration of treatment and follow-up were four days. Results There were no statistically significant differences in total markedly effective rate and total effective rate between RDQ group and LHQW group after treatment. Traditional Chinese Medicine (TCM) symptom score was significantly reduced after treatment in RDQ group, as well as in LHQW group. However, the difference of change in TCM symptom score between two groups was not statistically significant (P > 0.05). There were no significant differences between two groups in the median time to fever relief [RDQ group (4 ± 8) h vs LHQW group (4 ± 5) h] or the median time to fever clearance (RDQ group 47 h vs LHQW 36 h). No serious adverse events were reported during the study. Conclusion Compared with Lianhuaqingwen capsules, Reduqing granules achieved similar therapeutic effect in the treatment of CCWHS and no drug-related adverse events were reported during the study. Therefore, Reduqing granules might be effective and safe in the treatment of CCWHS.


title: Evaluation of preparedness of healthcare student volunteers against Middle East respiratory syndrome coronavirus (MERS-CoV) in Makkah, Saudi Arabia: a cross-sectional study

text: AIM: To assess the knowledge and attitude of senior medical, dental, nursing and pharmacy students toward Middle East respiratory syndrome-corona virus (MERS-CoV) in Saudi Arabia. SUBJECTS AND METHODS: A cross-sectional survey using a 21-item questionnaire was conducted for a 3-month period from November 2015–January 2016 in Makkah, Saudi Arabia. The questionnaire was designed to evaluate students’ understanding and perception of MERS-CoV. An ANOVA test was used to determine the association of study discipline and academic year with the student knowledge score on MERS. RESULTS: A total of 364 students were assessed during the study. The majority (62%) of the participants were in the 20–22-year age group. More than half (53%) were pharmacy students followed by (22%) medical students. More than two thirds (71%) of the participants were aware that MERS is caused by the coronavirus. More than half (59%) of the participants believed that MERS can be transmitted through direct or indirect contact with infected camels. A statistically significant association was reported between the study discipline and mean knowledge score (p < 0.0001) with medical students achieving an overall better knowledge score compared with students from other study disciplines. CONCLUSION: Overall, students had good knowledge about MERS epidemiology, transmission and the recommended protective measures. However, students expressed their reluctance to work in healthcare facilities with inadequate MERS infection control isolation policies.


title: Patient factors that affect trust in physicians: a cross-sectional study

text: BACKGROUND: While trust in physicians has been rigorously investigated regarding its concept, measurement, and factors, the studies have mainly focused on the attributes of the physicians. This approach can lead to a limited understanding of trust in physicians as trust is based on the relationship, an interaction of both parties: patients and physicians. This study aimed to investigate the factors for trust in physicians among the Koreans by focusing on patients’ traits which are related to their subjective perceptions. METHODS: A web-based survey was conducted between August and September 2016 among 1000 Korean adults aged 18 to 59 years. Survey participants were selected by a proportionate quota sampling based on age, sex and place of residence. The t-test and analysis of variance (ANOVA) were performed to examine the difference in trust in physicians among the different groups in each variable of patient characteristics. An ordinal logistic regression model was employed to examine the association between trust in physicians and patient attributes. RESULTS: Negative health-related traits, such as stress and low self-rated health, were likely to lower trust in physicians, and women were less likely to trust physicians. The negative attitudes toward the current health care system were strongly associated with low trust in physicians. Meanwhile, recent experience of hospitalization or outpatient visit was positively associated with trust in physicians, and experience of not being able to use health facilities showed no significant association. These results suggest that trust in physicians is more likely to be lowered by negative perception than by the objective conditions or experience. CONCLUSION: In investigating the factors for trust in physicians, the patients’ predispositions, which make them less likely to trust physicians, should be considered. The attributes of the patients in Korea, which could negatively affect trust in physicians, need to be investigated in consideration of the recent changes in patient-physician relationships and the medical environment in Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12875-018-0875-6) contains supplementary material, which is available to authorized users.


title: Head-tracking as an interface device for image control in digital pathology: a comparative study

text: BACKGROUND: Inasmuch as the conventional mouse is not an ideal input device for digital pathology, the aim of this study was to evaluate alternative systems with the goal of identifying a natural user interface (NUI) for controlling whole slide images (WSI). DESIGN: Four pathologists evaluated three webcam-based, head-tracking mouse emulators: Enable Viacam (eViacam, CREA Software), Nouse (JLG Health Solutions Inc), and Camera Mouse (CM Solutions Inc). Twenty WSI dermatopathological cases were randomly selected and examined with Image Viewer (Ventana, AZ, USA). The NASA-TLX was used to rate the perceived workload of using these systems and time was recorded. In addition, a satisfaction survey was used. RESULTS: The mean total time needed for diagnosis with Camera Mouse, eViacam, and Nouse was 18’57“, 19’37” and 22’32“, respectively (57/59/68 seconds per case, respectively). The NASA-TLX workload score, where lower scores are better, was 42.1 for eViacam, 53.3 for Nouse and 60.62 for Camera Mouse. This correlated with the pathologists’ degree of satisfaction on a scale of 1-5: 3.4 for eViacam, 3 for Nouse, and 2 for Camera Mouse (p< 0.05). CONCLUSIONS: Head-tracking systems enable pathologists to control the computer cursor and virtual slides without their hands using only a webcam as an input device. - Of the three software solutions examined, eViacam seems to be the best of those evaluated in this study, followed by Nouse and, finally, Camera Mouse. - Further studies integrating other systems should be performed in conjunction with software developments to identify the ideal device for digital pathology.


title: Diabetes management and specific considerations for patients with diabetes during coronavirus diseases pandemic: A scoping review

text: BACKGROUND AND AIMS: The global pandemic of coronavirus (COVID-19) affects almost all countries in the world, which potentially alter diabetes management. Many diabetes patients are experiencing barrier of care due to the policy related to COVID-19. This article aims to review the current evidence on diabetes management and specific consideration during the COVID-19 pandemic for people living with diabetes. METHODS: We conducted a scoping review in PubMed, Science Direct, DOAJ and Microsoft Academics databases from January 1 to April 17, 2020. Searching terms included “COVID-19", “severe acute respiratory syndrome coronavirus 2", and “Diabetes Mellitus” were used. Only scientific articles discussing diabetes management and specific considerations were selected and extracted. RESULTS: A total of 7 articles was selected in the analysis. Most were published in diabetes journals (85.71%). All articles (100%) discussed diabetes management and 71.43% of them provided diabetes care in specific considerations. We discussed issue of diabetes management in glycemic control and monitoring, dietary intake, physical activity, medication, education and prevention of COVID-19 infection that applicable for diabetes patients. In addition, specific considerations explored caring for diabetes in children and adolescents, pregnancy, elderly, emergency or critical care, to offer certain concern for raising the awareness. CONCLUSIONS: This review specifies a summary of diabetes management as well as the particular considerations to care people living with diabetes during COVID-19 pandemic. Patients, health care providers, and policy makers could take advantage of the review to assist diabetic people passing through COVID-19 pandemic session with optimum glycemic outcome.


title: Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease

text: Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as CXCL12) is perhaps an increasingly recognized target, given its importance in processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the current review, we will summarize the importance of DPP4-mediated enzymatic processing of cytokines/chemokines with an emphasis on SDF-1 and resultant implications for cardiovascular physiology and disease.


title: The role of the orthopaedic surgeon in the COVID-19 era: cautions and perspectives

text: The current coronavirus disease 2019 (COVID-19) pandemic has revolutionized global healthcare in an unprecedented way and with unimaginable repercussions. Resource reallocation, socioeconomic confinement and reorganization of production activities are current challenges being faced both at the national and international levels, in a frame of uncertainty and fear. Hospitals have been restructured to provide the best care to COVID-19 patients while adopting preventive strategies not to spread the infection among healthcare providers and patients affected by other diseases. As a consequence, the concept of urgency and indications for elective treatments have been profoundly reshaped. In addition, several providers have been recruited in COVID-19 departments despite their original occupation, resulting in a profound rearrangement of both inpatient and outpatient care. Orthopaedic daily practice has been significantly affected by the pandemic. Surgical indications have been reformulated, with elective cases being promptly postponed and urgent interventions requiring exceptional attention, especially in suspected or COVID-19(+) patients. This has made a strong impact on inpatient management, with the need of a dedicated staff, patient isolation and restrictive visiting hour policies. On the other hand, outpatient visits have been limited to reduce contacts between patients and the hospital personnel, with considerable consequences on post-operative quality of care and the human side of medical practice. In this review, we aim to analyze the effect of the COVID-19 pandemic on the orthopaedic practice. Particular attention will be dedicated to opportune surgical indication, perioperative care and safe management of both inpatients and outpatients, also considering repercussions of the pandemic on resident education and ethical implications.


title: Detecting amplicons of loop‐mediated isothermal amplification

text: Loop‐mediated isothermal amplification (LAMP) assays are used to detect diverse pathogens. Initially, LAMP amplicons were detected using electrophoresis; later, real‐time monitoring based on turbidity was developed to overcome the problem of contamination with environmental DNA. Recently, real‐time monitoring of fluorescence signals using a quenching primer and probe has improved the reliability of amplification signals. Here, methods of detecting LAMP amplicons are reviewed.


title: Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore

text: BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern—a week after Singapore’s first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore’s third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt—undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation’s first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.


title: What do we know about COVID-19? A review article

text: OBJECTIVES: To bring summarized information about what has been published so far regarding Covid-19, facilitating the access to information and a better understanding of this pandemic, and to contribute to the medical community in the decision-making against this virus METHODS: This review article brings collected information from different articles published since the beginning of the pandemic of the 2019 novel coronavirus KEY RESULTS: This paper aggregates and consolidates some epidemiological parameters and clinical knowledge about the novel coronavirus and brings what is new in the search for pandemic control MAJOR CONCLUSIONS: Governments and health authorities are under increased pressure to control the COVID-19 spreading In this scenario, the scientific community is working hard to produce relevant papers which will help in the next steps against coronavirus Our review summarized the latest news about SARS-CoV2, evidencing what we know about COVID-19 until now


title: Workplace responses to COVID‐19 associated with mental health and work performance of employees in Japan

text: OBJECTIVES: The study investigated the links between workplace measures implemented in response to COVID‐19 with mental health and work performance of employees in Japan. METHODS: This was a cross‐sectional study of a sample from a cohort study of full‐time employees. Participants (n = 1448) completed an online self‐report questionnaire on March 19‐22, 2020. Multiple linear regression was conducted to ascertain their fear of and worry associated with COVID‐19, psychological distress, and work performance. RESULTS: The number of workplace measures correlated positively with respondents' fear of and worry associated with COVID‐19 (adjusted standardized β = 0.123, P < .001), negatively with psychological distress and positively with work performance (adjusted standardized β = −0.068, P = .032; adjusted standardized β = 0.101, P = .002; respectively). CONCLUSIONS: Workplace measures may promote and maintain the mental health and work performance of employees during the COVID‐19 epidemic. The positive association between the number of measures and fear and worry about COVID‐19 may reflect increased awareness about COVID‐19 among employees resulted from taking the measures.


title: Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description

text: BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti–MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti–MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.


title: Viruses causing lower respiratory symptoms in young children: findings from the ORChID birth cohort

text: INTRODUCTION: Viral acute respiratory infections (ARIs) cause substantial child morbidity. Sensitive molecular-based assays aid virus detection, but the clinical significance of positive tests remains uncertain as some viruses may be found in both acutely ill and healthy children. We describe disease-pathogen associations of respiratory viruses and quantify virus-specific attributable risk of ARIs in healthy children during the first 2 years of life. METHODS: One hundred fifty-eight term newborn babies in Brisbane, Australia, were recruited progressively into a longitudinal, community-based, birth cohort study conducted between September 2010 and October 2014. A daily tick-box diary captured predefined respiratory symptoms from birth until their second birthday. Weekly parent-collected nasal swabs were batch-tested for 17 respiratory viruses by PCR assays, allowing calculation of virus-specific attributable fractions in the exposed (AFE) to determine the proportion of virus-positive children whose ARI symptoms could be attributed to that particular virus. RESULTS: Of 8100 nasal swabs analysed, 2646 (32.7%) were virus-positive (275 virus codetections, 3.4%), with human rhinoviruses accounting for 2058/2646 (77.8%) positive swabs. Viruses were detected in 1154/1530 (75.4%) ARI episodes and in 984/4308 (22.8%) swabs from asymptomatic periods. Respiratory syncytial virus (AFE: 68% (95% CI 45% to 82%)) and human metapneumovirus (AFE: 69% (95% CI 43% to 83%)) were strongly associated with higher risk of lower respiratory symptoms. DISCUSSION: The strong association of respiratory syncytial virus and human metapneumovirus with ARIs and lower respiratory symptoms in young children managed within the community indicates successful development of vaccines against these two viruses should provide substantial health benefits.


title: Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells

text: BACKGROUND: Herpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells, critical for viral replication, is being extensively investigated by many laboratories. In this study, we tested the hypothesis that HSV-1 lytic infection triggers the expression of important multi-functional transcription factor Egr1. The mechanisms of induction are mediated, at least in part, by signaling pathways such as NFκB and CREB. METHODS: SIRC, VERO, and 293HEK cell lines were infected with HSV-1, and the Egr-1 transcript and protein were detected by RT-PCR and Western blot, respectively. The localization and expression profile of Egr-1 were investigated further by immunofluorescence microscopy analyses. The recruitment of transcription factors to the Egr-1 promoter during infection was studied by chromatin immunoprecipitation (ChIP). Various inhibitors and dominant-negative mutant were used to assess the mechanisms of Egr-1 induction and their effects were addressed by immunofluorescence microscopy. RESULTS: Western blot analyses showed that Egr-1 was absent in uninfected cells; however, the protein was detected 24-72 hours post treatment, and the response was directly proportional to the titer of the virus used for infection. Using recombinant HSV-1 expressing EGFP, Egr-1 was detected only in the infected cells. ChIP assays demonstrated that NFкB and cAMP response element binding protein (CREB) were recruited to the Egr-1 promoter upon infection. Additional studies showed that inhibitors of NFкB and dominant-negative CREB repressed the Egr-1 induction by HSV-1 infection. CONCLUSION: Collectively, these results demonstrate that Egr-1 is expressed rapidly upon HSV-1 infection and that this novel induction could be due to the NFкB/CREB-mediated transactivation. Egr-1 induction might play a key role in the viral gene expression, replication, inflammation, and the disease progression.


title: Aus Angst vor Corona nicht zum Arzt?: Drohende Versorgungskrise

text: Die grassierende Angst, sich beim Arztkontakt mit SARS-CoV-2 zu infizieren, ist per se ein Risikofaktor: Sie hält derzeit offenbar viele Menschen davon ab, sich bei akuten Beschwerden in einer Klinik oder Praxis vorzustellen.


title: Co‐localization of Middle East respiratory syndrome coronavirus (MERS‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas

text: This study investigated the co‐localization of the Middle East respiratory syndrome coronavirus (MERS‐CoV) and its receptor dipeptidyl peptidase‐4 (DPP4) by immunohistochemistry (IHC) across respiratory and lymphoid organs of experimentally MERS‐CoV infected pigs and llamas. Also, scanning electron microscopy was performed to assess the ciliary integrity of respiratory epithelial cells in both species. In pigs, on day 2 post‐inoculation (p.i.), DPP4‐MERS‐CoV co‐localization was detected in medial turbinate epithelium. On day 4 p.i., the virus/receptor co‐localized in frontal and medial turbinate epithelial cells in pigs, and epithelial cells distributed unevenly through the whole nasal cavity and in the cervical lymph node in llamas. MERS‐CoV viral nucleocapsid was mainly detected in upper respiratory tract sites on days 2 and 4 p.i. in pigs and day 4 p.i. in llamas. No MERS‐CoV was detected on day 24 p.i. in any tissue by IHC. While pigs showed severe ciliary loss in the nasal mucosa both on days 2 and 4 p.i. and moderate loss in the trachea on days 4 and 24 p.i., ciliation of respiratory organs in llamas was not significantly affected. Obtained data confirm the role of DPP4 for MERS‐CoV entry in respiratory epithelial cells of llamas. Notably, several nasal epithelial cells in pigs were found to express viral antigen but not DPP4, suggesting the possible existence of other molecule/s facilitating virus entry or down regulation of DPP4 upon infection.


title: Molecular epidemiology of porcine epidemic diarrhea virus in China

text: Since early 2006, porcine epidemic diarrhea virus (PEDV) has been reemerging in immunized swine herds. Open reading frame 3 (ORF3) is the only accessory gene in the PEDV genome. The entire ORF3 genes of 12 PEDV field strains and one vaccine strain were sequenced. The ORF3 genes of Chinese PEDV field strains (excluding CH/GSJIII/07) contain a single 672- or 675-nucleotide (nt) ORF, which encodes a 223- or 224-aa-long peptide. However, the CV777 vaccine strain and CH/GSJIII/07 contain a 276-nt ORF because of a 49-nt deletion at nt 245–293. The Chinese PEDV field strains and PEDV reference strains are divided into three groups based on the phylogenetic relationship of their ORF3 genes. Chinese PEDV field strains (excluding CH/GSJIII/07) have a close phylogenetic relationship to Korean strains and are genetically different from the PEDV vaccine strains. However, CH/GSJIII/07 has a close phylogenetic relationship to two vaccine strains, suggesting that it might have evolved from a live vaccine strain. Chinese PEDV field strains (excluding CH/GSJIII/07) can be differentiated from PEDV vaccine strains by a nested RT-PCR method.


title: Ethnoveterinary medicines used for ruminants in British Columbia, Canada

text: BACKGROUND: The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. METHODS: In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. RESULTS: There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera helix and Alchemilla vulgaris are fed for retained placenta. CONCLUSION: Some of the plants showing high levels of validity were Hedera helix for retained placenta and Euphrasia officinalis for eye problems. Plants with high validity for wounds and injuries included Hypericum perforatum, Malva parviflora and Prunella vulgaris. Treatments with high validity against endoparasites included those with Juniperus communis and Pinus ponderosa. Anxiety and pain are well treated with Melissa officinalis and Nepeta caesarea.


title: Fatal Gastrointestinal Infection with ‘Flexispira rappini’‐Like Organisms in a Cat

text: A 4‐month‐old male British Blue cat with catarrhal to haemorrhagic enteritis showed massive colonization of the stomach, small intestine and caecum with spiral‐shaped bacilli. In the stomach, organisms were located in foveolae and gland lumina and within unaltered and degenerate epithelial cells. Inflammatory infiltration was moderate and T cell dominated. In the intestine, bacilli were found in the gut lumen, between villi, in crypt lumina and within epithelial cells. Degeneration of crypt epithelial cells as well as crypt dilation and moderate to massive macrophage‐dominated infiltration of the mucosa and submucosa were observed. Immunohistochemically, bacilli were positive with an antibody against Helicobacter. Ultrastructurally, the organisms strongly resembled ‘Flexispira rappini’, a spiral‐shaped Helicobacter species known as a normal intestinal colonizer in dogs and mice.


title: Predominant Bacteria Detected from the Middle Ear Fluid of Children Experiencing Otitis Media: A Systematic Review

text: BACKGROUND: Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. METHODS: A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. RESULTS: This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. CONCLUSIONS: Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.


Surveillance, intelligence, and intuition: Knowing when to re‐engage in clinical operations


title: Biomarkers of lung‐related diseases: Current knowledge by proteomic approaches

text: The lung epithelial surface is one of the vital barriers or sensors in the body responding to the external atmosphere and thereby always subjecting to direct toxicological exposure, stress, stimulus, or infection. Due to its relatively higher sensitivity in response to toxicants, the use of lung epithelial cell culture and lung tissue from animal models or patients has facilitated our learning to lung physiopathology and toxicopharmacology. The recent advancement of proteomics has made it possible to investigate the cellular response at a global level. In this review, the potential applications of proteomic approach in studying lung‐related diseases and biomarker discovery will be discussed. J. Cell. Physiol. 221: 535–543, 2009. © 2009 Wiley‐Liss, Inc.


title: Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future

text: The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.