title: Selective expansion of intraepithelial lymphocytes expressing the HLA-E–specific natural killer receptor CD94 in celiac disease

text: Abstract Background & Aims: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4+ T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. Methods: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. Results: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94+ IELs, which were mostly αβ T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. Conclusions: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E–specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion. GASTROENTEROLOGY 2000;118:867-879


title: Clustered Cases of Acral Perniosis: Clinical Features, Histopathology and Relationship to COVID‐19

text: BACKGROUND/OBJECTIVES: There has been a recent marked increase in pediatric and adult patients presenting with purpuric acral lesions concerning for ischemia, thrombosis and necrosis in COVID‐19 prevalent regions worldwide. The clinical and histopathological features and relationship to COVID‐19 have not been well described. The objective of this case series is to describe the clinical features and determine the histopathologic findings and clinical implications of the clusters of acral perniosis cases identified in pediatric patients. METHODS: We describe 6 otherwise healthy adolescents – 3 siblings per family from 2 unrelated families – presented within a 48‐hour period in April, 2020, with acral perniosis‐like lesions in the context of over 30 similar patients who were evaluated within the same week. RESULTS: Affected patients had mild symptoms of viral upper respiratory infection (URI) or contact with symptomatic persons 1‐2 weeks preceding the rash. They all presented with red to violaceous macules and dusky, purpuric plaques scattered on the mid and distal aspects of the toes. Skin biopsies performed on each of the 6 patients demonstrated near identical histopathologic findings to those of idiopathic perniosis, with a lymphocytic inflammatory infiltrate without evidence of thromboembolism or immune complex vasculitis. While SARS‐CoV‐2 polymerase chain reaction was negative, testing was performed 1‐2 weeks after URI symptoms or sick contact exposure. CONCLUSION: We offer a clinical approach to evaluation of patients with this presentation and discuss the possibility that these skin findings represent a convalescent‐phase cutaneous reaction to SARS‐CoV‐2 infection.


title: Protecting healthcare personnel from 2019-nCoV infection risks: lessons and suggestions

text: The outbreak of a novel Coronavirus disease (COVID-19, caused by the 2019-nCoV infection) in December 2019 is one of the most severe public health emergencies since the founding of People’s Republic of China in 1949. Healthcare personnel (HCP) nationwide are facing heavy workloads and high risk of infection, especially those who care for patients at the epicenter of the outbreak, Hubei Province. Sadly, as of February 20, 2020, over two thousand COVID-19 cases are confirmed among HCP from 476 hospitals nationwide, with nearly 90% of them from Hubei Province. Based on literature search and interviews with some HCP working at Wuhan, capital city of Hubei, we have summarized some of the effective measures taken to reduce infection among HCP, and also made suggestions for improving occupational safety during an infectious disease outbreak. The experience and lessons learned should be a valuable asset for international health community to contain the ongoing COVID-19 epidemic around the world.


title: Urbanization and the dynamics of RNA viruses in Mallards (Anas platyrhynchos)

text: Abstract Urbanization is intensifying worldwide, and affects the epidemiology of infectious diseases. However, the effect of urbanization on natural host-pathogen systems remains poorly understood. Urban ducks occupy an interesting niche in that they directly interact with both humans and wild migratory birds, and either directly or indirectly with food production birds. Here we have collected samples from Mallards (Anas platyrhynchos) residing in a pond in central Uppsala, Sweden, from January 2013 to January 2014. This artificial pond is kept ice-free during the winter months, and is a popular location where the ducks are fed, resulting in a resident population of ducks year-round. Nine hundred and seventy seven (977) fecal samples were screened for RNA viruses including: influenza A virus (IAV), avian paramyxovirus 1, avian coronavirus (CoV), and avian astrovirus (AstroV). This intra-annual dataset illustrates that these RNA viruses exhibit similar annual patterns to IAV, suggesting similar ecological factors are at play. Furthermore, in comparison to wild ducks, autumnal prevalence of IAV and CoV are lower in this urban population. We also demonstrate that AstroV might be a larger burden to urban ducks than IAV, and should be better assessed to demonstrate the degree to which wild birds contribute to the epidemiology of these viruses. The presence of economically relevant viruses in urban Mallards highlights the importance of elucidating the ecology of wildlife pathogens in urban environments, which will become increasingly important for managing disease risks to wildlife, food production animals, and humans.


title: Outbreak of Streptococcus equi subsp. zooepidemicus infection in a group of rhesus monkeys (Macaca mulatta)

text: Background A severe upper respiratory tract infection occurred in a breeding group of rhesus monkeys housed together in one of six indoor/outdoor corals of the German Primate Center. The clinical signs of the disease included severe purulent conjunctivitis, rhinitis, pharyngitis, respiratory distress and lethargy. Six of 45 animals died within a few days after developing signs of infection. Methods and results Histopathologic and microbiologic examinations of the dead animals were consistent with a severe fibrinopurulent bronchopneumonia. Microbiology revealed a Lancefield group C streptococcus identified as Streptococcus equi subsp. zooepidemicus as the causative agent of infection. Conclusions The infection was passed on from animal to animal but did not spread to the other five breeding groups nearby. Extensive diagnostic testing failed to reveal the consisting presence of copathogens in individual cases. A visitor with upper respiratory disease was suspected as source of infection.


title: SARS-CoV-2 infection in a patient on chronic hydroxychloroquine therapy: Implications for prophylaxis

text: Abstract People exposed to COVID-19 have a risk of developing disease, and health care workers are at risk at a time when they are badly needed during a health care crisis. Hydroxychloroquine and chloroquine have been used as treatment and are being considered as prophylaxis. Our patient developed COVID-19 while on hydroxychloroquine and although more work is needed, this calls into question the role of these medications as preventive therapy.


title: Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea

text: BACKGROUND: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0–18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2–18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.


title: A contribution to the ectoparasite fauna of bats (Mammalia: Chiroptera) in Mindoro Island, Philippines: I. Blood sucking Diptera (Nycteribiidae, Streblidae) and Siphonaptera (Ischnopsyllidae)

text: New data on bat ectoparasites from Mindoro Island, Philippines are reported. Eighty-three individuals of ectoparasitic insects representing seven species of Nyc-teribiidae and fve species of Streblidae (both Diptera), and one species of Ischnopsyllidae (Siphonaptera) were recorded from 11 bat species captured in Naujan Lake National Park, Mindoro Oriental Province, Philippines. Raymondia pagodarum is a new record for the country. Eight species are also newly recorded for Mindoro Island, including Cyclopodia garrula, Leptocyclopodia ferrarii mabuhai, Megastrebla parvior, Brachytarsina amboinensis, B. werneri, R. pagodarum, R. pseudopagodarum and Thaumapsylla longiforceps. Five species are newly documented on various hosts: C. horsfieldi on Pteropus pumilus, M. parvior on Macroglossus minimus, B. amboinensis on Hipposideros diadema, B. werneri on Rhinolophus arcuatus and R. pagodarum on Hipposideros bicolor.


title: Background K(2P) Channels KCNK3/9/15 Limit the Budding of Cell Membrane-derived Vesicles

text: The main function of background two-pore potassium (K(2P)) channels KCNK3/9/15 is to stabilize the cell membrane potential. We previously observed that membrane potential depolarization enhances the release of HIV-1 viruses. Because membrane polarization affects the biomembrane directly, here we examined the effects of KCNK3/9/15 on the budding of nonviral vesicles. We found that depolarization by knocking down endogenous KCNK3/9/15 promoted secretion of cell-derived vesicles. We further used Vpu (an antagonist of KCNK3) as a model for the in vivo study of depolarization-stimulated secretion. Vpu is a HIV-1-encoded, ion channel-like protein (viroporin) capable of enhancing virus release and depolarizing the cell membrane potential. We found that Vpu could also promote nonviral vesicle release, perhaps through a similar mechanism that Vpu utilizes to promote viral particle release. Notably, T cells expressing Vpu alone became pathologically low in intracellular K(+) and insensitive to extracellular K(+) or membrane potential stimulation. In contrast, heterologous expression of KCNK3 in T cells stabilized the cell potentials by maintaining intracellular K(+). We thus concluded that KCNK3/9/15 expression limits membrane depolarization and depolarization-induced secretion at least in part by maintaining intracellular K(+).


title: The etiologic role of infectious antigens in sarcoidosis pathogenesis

text: Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th1 immunophenotype, most commonly involving the lung, skin, lymph node and eyes. Molecular and immunologic studies continue to strengthen the association of sarcoidosis with infectious antigens, particularly those derived from Propionibacterium and Mycobacterium species. Independent studies report the presence of microbial nucleic acids and proteins within sarcoidosis specimens. Complementary immunologic studies also support the role of infectious agents in sarcoidosis pathogenesis. Th-1 immune responses directed against mycobacterial virulence factors have been detected within sarcoidosis diagnostic bronchoalveolar lavage (BAL). Th1 and Th17 immune responses against propionibacteria have also been reported. More recently, case reports and clinical trials from Japanese, European and American investigators have emerged regarding the efficacy of antimicrobials against Propionibacterium and Mycobacterium species on pulmonary and cutaneous sarcoidosis. While these clinical investigations are not conclusive, they support increasing efforts to identify novel therapeutics, such as antimicrobials, that will impact the observed increase in sarcoidosis morbidity and mortality.


title: Pandemic and Bank Lending: Evidence from the 2009 H1N1 Pandemic

text: This paper empirically analyzes the impact of pandemic on the contracting of bank loans. Using data on syndicated loans during the season of H1N1 Swine Flu, we find that more flu is associated with higher loan spreads and smaller loan size. The adverse impact of pandemic was alleviated by the approval of vaccines.


title: Patterns of HIV and SARS‐CoV‐2 co‐infection in Wuhan, China

text: People living with HIV/AIDS (PLWHA) were initially considered to be at an increased risk of infection with SARS‐CoV‐2 due to their risk of immunosuppresion(1). However, few studies have reported on co‐infections between HIV and SARS‐CoV‐2 and treatment outcomes, and data to date do not support either increased acquisition or severity of COVID‐19.


title: CD4 T cells control development and maintenance of brain-resident CD8 T cells during polyomavirus infection

text: Tissue-resident memory CD8 T (T(RM)) cells defend against microbial reinfections at mucosal barriers; determinants driving durable T(RM) cell responses in non-mucosal tissues, which often harbor opportunistic persistent pathogens, are unknown. JC polyomavirus (JCPyV) is a ubiquitous constituent of the human virome. With altered immunological status, JCPyV can cause the oft-fatal brain demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV is a human-only pathogen. Using the mouse polyomavirus (MuPyV) encephalitis model, we demonstrate that CD4 T cells regulate development of functional antiviral brain-resident CD8 T cells (bT(RM)) and renders their maintenance refractory to systemic CD8 T cell depletion. Acquired CD4 T cell deficiency, modeled by delaying systemic CD4 T cell depletion until MuPyV-specific CD8 T cells have infiltrated the brain, impacted the stability of CD8 bT(RM), impaired their effector response to reinfection, and rendered their maintenance dependent on circulating CD8 T cells. This dependence of CD8 bT(RM) differentiation on CD4 T cells was found to extend to encephalitis caused by vesicular stomatitis virus. Together, these findings reveal an intimate association between CD4 T cells and homeostasis of functional bT(RM) to CNS viral infection.


title: Donning a new approach to the practice of gastroenterology: perspectives from the COVID-19 pandemic epicenter

text: Abstract The COVID-19 pandemic is seemingly peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving (personal protective equipment) PPE, and freeing hospital beds have driven unconventional approaches to managing GI patients. Conversion of endoscopy units to COVID units and redeployment of gastroenterology (GI) fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been drastically reduced. In this review we share our collective experiences, how we have changed our practice of medicine, in response to the COVID surge. While we will review our management of specific consults and conditions, the overarching theme focuses primarily on non-invasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, while always important, has now become critical. And the support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and foster trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our “new normal.”


docid: uyslahhk

title: Endoscopic skull base and transoral surgery during COVID‐19 pandemic: Minimizing droplet spread with negative‐pressure otolaryngology viral isolation drape

text: BACKGROUND: The coronavirus disease (COVID‐19) pandemic has raised concern of transmission of infectious organisms through aerosols formation in endonasal and transoral surgery. METHODS: Retrospective review. We introduce the negative‐pressure otolaryngology viral isolation drape (NOVID) system to reduce the risk of aerosol. NOVID consists of a plastic drape suspended above the patient's head and surgical field with a smoke evacuator suction placed inside the chamber. RESULTS: Four patients underwent endonasal (4) and endo‐oral surgery (1). Fluorescein was applied to the surgical field. Black light examination of fluorescein‐treated operative fields revealed minimal contamination distant to the surgical field. In two prolonged cases with high‐speed drilling, droplets were identified under the barrier and on the tip of the smoke evacuator. Instruments and cottonoids appeared to be a greater contributor to field contamination. CONCLUSIONS: Negative‐pressure aspiration of air under a chamber barrier, which appears to successfully keep aerosol and droplet contamination to a minimum.


title: A cis-Acting Viral Protein Is Not Required for the Replication of a Coronavirus Defective-Interfering RNA

text: Abstract Mouse hepatitis virus (MHV), a coronavirus, generates defective-interfering (DI) RNAs of different sizes during passages at high multiplicities of infection. All MHV DI RNAs characterized so far contain an open reading frame (ORF) encoding a fused viral protein; in addition, DI RNAs with a long ORF have a competitive advantage over those with a shorter ORF. These findings suggest that DI RNA replication may require an ORF encoding a cis-acting viral protein. In this study, we used a naturally occurring DI RNA and inserted a 12-nucleotide (nt) amber-mutation linker at various positions to truncate the ORF. Most of the mutants replicated as well as the wild-type DI RNA, irrespective of the presence or absence and the length of the ORF in the RNA. Sequence analysis showed that all of the mutants retained the insertional mutations even after two viral passages in tissue culture, establishing that the mutant DI RNAs replicated. We have further introduced two 3-nucleotide substitutions of the first two AUG codons of the ORF, thus completely closing the ORF. This DI RNA replicated as well as the wild-type DL but, after a single passage, the majority of the mutant RNAs was replaced by recombinant RNAs which contain a restored functional ORF. However, an additional insertion of a 12-nt amber-mutation linker downstream of the AUG substitutions prevented recombination, and the DI RNA still replicated. These data indicate that DI RNA replication does not require a DI-specific ORF encoding cis-acting viral proteins and that a 12-nucleotide insertion could prevent or delay the occurrence of RNA recombination, suggesting the importance of direct or indirect RNA alignment in homologous RNA recombination.


title: Why the vision of interregional electric transmission development in FERC Order 1000 is not happening

text: Abstract The Federal Energy Regulatory Commission (FERC) on March 19, 2020 announced a Notice of Proposed Rulemaking (NOPR) i i FERC Docket RM20-10-000. to further investigate how financial incentives might be used to encourage development of high-voltage electric transmission in the United States. An extension of previous efforts in FERC Order 679 issued in 2006, the NOPR-proposed incentives would consist of up to 250 additional basis points of equity return to be allowed on qualifying transmission projects. The NOPR was published in the Federal Register on April 2, and public comments were due back to FERC by July 1. Such incentives, if adopted, would be helpful to address prior FERC business that is yet undone. Issued in 2011, FERC Order 1000, “Transmission and Cost Allocation by Transmission Owning and Operating Utilities” among other things envisioned coordinated planning of interregional transmission developments spanning between individual Regional Transmission Organizations (RTO) and Independent System Operators (ISO), the operators of the FERC-regulated organized wholesale markets. In addition to traditional goals of generator interconnection and service reliability, the purpose of such interregional transmission development was to support public policy goals including renewable energy development, and lower costs for consumers. But little or no such interregional development has happened since Order 1000. Why? The authors have spent the last several years promoting development of one such interregional transmission project. While the effort is ongoing, the on-the-ground experience to-date clearly shows the reasons why interregional development envisioned by FERC Order 1000 is not happening. The authors offer solutions to the issues, including how the new FERC NOPR for transmission incentives can be helpful.


Infectious disease aerobiology: miasma incarnate


title: The puzzle of RNA recombination

text: Abstract For more than three decades, RNA recombination remained a puzzle and has only begun to be solved in the last few years. The available data provide evidence for a variety of RNA recombination mechanisms. Non-homologous recombination seems to be the most common for RNA. Recent experiments in both the in vitro and the in vivo systems indicate that this type of recombination may result from various transesterification reactions which are either performed by RNA molecules themselves or are promoted by some proteins. The high frequency of homologous recombination manifested by some RNA viruses can be easier explained by a replicative template switch.


MERS—the latest threat to global health security


title: Synthesis paradigm and applications of silver nanoparticles (AgNPs), a review

text: Abstract Nanoscience is an inspiring and influential discipline of science which have accessible numerous novel and cost-effective yields and applications. Currently, nanotechnology research has been empowering more in agricultural sector, food process and medicinal industries. The surface area to volume ratio of nanoparticles is quite large which have 1–100nm size. Nanomaterials have superior bioavailability than larger particles, resulting in greater utilization in single cells, tissues and organs. Referable to the growing demand of nanoparticles, it is essential to build up synthetic method which is profitable, environmentally sustainable and which can substitutes with effective and competent technology to synthesis environmentally benign nanoparticles (NPs). Nanomaterials are “deliberately engineered” to direct the enhancement of special properties at the nanoscale. Nanoparticles have been known to be used for abundant physical, biological, and pharmaceutical applications. Nano-silver is the most studied and utilized nanoparticle. Silver nanoparticles (AgNPs) have been the topics of researchers because of their unique properties. Thus, this review presents various synthesis methods of AgNPs and its application in different sectors.


title: Mobilizing the research ecosystem for scientific advances towards positive impact in the context of the COVID-19 Pandemic

text: This special issue of the Turkish Journal of Medical Sciences is dedicated to providing scientific advances in the process of better understanding the SARS-CoV-2 virus that causes the COVID-19 infection. The special issue is published in a special time in which science-based approaches, cocreation-based collaboration, and the effective utilization and integration of competences have a crucial role during the race against time while combating the COVID-19 pandemic. In this process, the Scientific and Technological Research Council of Turkey (TÜBİTAK), which publishes academic journals including the Turkish Journal of Medical Sciences, has taken rapid action to mobilize the research community. This includes forming new scientific coalitions in record time, the opening of new calls across the research ecosystem, the organization of a virtual scientific conference, and the launch of a new portal in support of cocreation processes and open science. In addition, various teleconferences that bring together various disciplines at the national and international level have taken place. All of these efforts provide multiple venues to support the common effort of combating the COVID-19 pandemic with R&D and development as a common objective. The sharing of evidence-based knowledge and scientific progress is an effective approach towards providing important contributions for combating the COVID-19 pandemic. The research articles that are contained in this special issue of the Turkish Journal of Medical Sciences involves a special collection dedicated to COVID-19. This short communication aims to provide an introduction of the major initiatives that have been taken in the scientific landscape with a focus on Turkey.


title: Do adaptive immune cells suppress or activate innate immunity?

text: Current dogma holds that the innate immune system primes the adaptive immune system in response to infection, which in turn amplifies innate responses in a positive loop to effectively control pathogens. Therefore, it is accepted in most cases that T-cell deficient hosts die of acute infection because of the impaired ability of the innate immune system to control pathogens. Recent studies, however, reveal that adaptive immune cells actively dampen initial innate responses. In contrast to current understanding, there is now evidence that an insufficient number of T cells results in loss of control of innate immune responses. This raises new questions regarding the, as of yet underappreciated, role of the adaptive immune system in early infection and inflammation.


title: Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

text: Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL(−1), with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.


Otorhinolaryngology, head and surgery practice during the COVID-19 pandemic


title: First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease

text: The association between coronaviruses and central nervous system (CNS) demyelinating lesions has been previously shown. However, no case has been described of an association between the novel coronavirus (SARS-COV-2) and CNS demyelinating disease so far. SARS-COV-2 was previously detected in cerebrospinal fluid (CSF) sample of a patient with encephalitis. However, the virus identity was not confirmed by deep sequencing of SARS-COV-2 detected in the CSF. Here, we report a case of a patient with mild respiratory symptoms and neurological manifestations compatible with clinically isolated syndrome. The viral genome of SARS-COV-2 was detected and sequenced in CSF with 99.74–100% similarity between the patient virus and worldwide sequences. This report suggests a possible association of SARS-COV-2 infection with neurological symptoms of demyelinating disease, even in the absence of relevant upper respiratory tract infection signs.


Could renin–angiotensin–aldosterone system inhibitors be used for hypertensive patients with coronavirus disease 2019?


title: H5N1 Oseltamivir-resistance detection by real-time PCR using two high sensitivity labeled TaqMan probes

text: Abstract A single amino acid substitution, from histidine to tyrosine at position 274 of the neuraminidase gene has converted Oseltamivir sensitive H5N1 influenza A virus into a resistant strain. Currently, Oseltamivir is being stockpiled in many countries potentially affected by the influenza A virus subtype H5N1 epidemic. To identify this change in Oseltamivir-treated patients, a method based on real-time PCR using two labeled TaqMan probes was developed for its rapid detection. In order to validate the method, Oseltamivir specimen from treated (Oseltamivir-resistant strain from a Vietnamese patient, two Oseltamivir-treated tigers) and untreated subjects have been used for this study. The results thus obtained as well as those derived from clone selection and sequencing showed that TaqMan probes could clearly discriminate wild type H274 from the mutant 274Y variant. The sensitivity of this assay was as low as 10 copies/μl and allowed the detection of the mutation in a mixture of wild type and mutant. Overall, the assay based on real-time PCR with two labeled TaqMan probes described here should be useful for detecting Oseltamivir-resistant H274Y H5N1 influenza A virus in many species and various sources of specimens with high sensitivity and specificity. Such studies can address potential differences in the diagnostic outcomes between patients who develop detectable Oseltamivir resistance and those who retain only the wild type strain of H5N1.


COVID‐19 and economy


Lichenoid eruptions with interface dermatitis and necrotic subepidermal blister associated with COVID‐19


title: Advances in Diagnostic Approaches for Viral Etiologies of Diarrhea: From the Lab to the Field

text: The applications of correct diagnostic approaches play a decisive role in timely containment of infectious diseases spread and mitigation of public health risks. Nevertheless, there is a need to update the diagnostics regularly to capture the new, emergent, and highly divergent viruses. Acute gastroenteritis of viral origin has been identified as a significant cause of mortality across the globe, with the more serious consequences seen at the extremes of age groups (young and elderly) and immune-compromised individuals. Therefore, significant advancements and efforts have been put in the development of enteric virus diagnostics to meet the WHO ASSURED criteria as a benchmark over the years. The Enzyme-Linked Immunosorbent (ELISA) and Polymerase Chain Reaction (PCR) are the basic assays that provided the platform for development of several efficient diagnostics such as real-time RT-PCR, loop-mediated isothermal amplification (LAMP), polymerase spiral reaction (PSR), biosensors, microarrays and next generation sequencing. Herein, we describe and discuss the applications of these advanced technologies in context to enteric virus detection by delineating their features, advantages and limitations.


title: Searching for the elusive typhoid diagnostic

text: Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.


title: Chapter 4 Human Viruses: Emergence and Evolution

text: Abstract Many new viruses have emerged in the last five decades. These newer genetically active agents have a major impact on the public health systems worldwide. Most emerging infections appear to be caused by pathogens already present in the environment, brought out of obscurity or given a selective advantage by changing conditions and afforded an opportunity to infect new host populations. Also on rare occasions, a new variant may evolve and cause a new disease. Altered virus transmission because of deforestation and environment change, ecological changes and agricultural development, commerce, technology, microbial adaptation and change, breakdown of public health measures, and deficiencies in public health infrastructure are the reasons for emergence and reemergence of infectious diseases in general and viral infections in particular. Specific factors precipitating disease emergence can be identified in virtually all cases. Moreover, these factors are increasing in prevalence. This increase, together with the ongoing evolution of viral and microbial variants and selection for drug resistance, suggests that infections will continue to emerge and probably increase and emphasize the urgent need for effective surveillance and control. These viruses are rich source of emerging diseases due to the introduction of infections from other species in the zoonotic pool. In the near future, there is an urgent need to monitor collaboration between human–animal interface so that public health risks can be understood. A number of activities increase microbial traffic from animals to humans or disseminate microbes from isolated groups into new populations and as a result promote emergence and epidemics. In some cases, including many of the most novel infections, the agents are zoonotic crossing from their natural hosts into the human population because of many similarities. Vector-borne diseases also have a natural advantage of dissemination.


title: Psychological effects of nurses and midwives due to COVID-19 outbreak: The case of Turkey

text: PURPOSE: The study was carried out to determine the psychological impact levels of nurses and midwives due to the COVID-19 outbreak. METHODS: The research is planned in a descriptive type. Nurses and midwives working in any health institution in Turkey constituted the population of the research. The questionnaire form of the study was shared on social media tools between 01 and 14 April 2020 and a total of 758 nurses and midwives were included in the study sample. Personal Information Form, State-Trait Anxiety Inventory and Intolerance of Uncertainty Scale were used as data collection tools. RESULTS: Participants who attended the study were 56.9% of nurses and 43.1% of midwives. Approximately half of the nurses and midwives (48.8%) participating in our study contacted the patient with suspected COVID-19, and 29.8% provided care to the patient diagnosed with COVID-19. Nurses and midwives were scored 52.75 ± 9.80 for State Anxiety, 44.87 ± 7.92 for Trait Anxiety Inventory and 35.16 ± 9.42 for Intolerance of Uncertainty Scale. It has been determined that 54.5% of nurses and midwives have been making their lives worse since the outbreak started, 62.4% had difficulties in dealing with the uncertain situation in the outbreak, 42.6% wanted psychological support and 11.8% had alienated from their profession. It was determined that there was a difference between scale scores and difficulties in work, family and private life due to COVID-19. CONCLUSION: As a result, it is seen that the midwives and nurses in our country have high psychological effects due to the COVID-19 outbreak.


title: The Identification and Characterization of Two Novel Epitopes on the Nucleocapsid Protein of the Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death, particularly in neonatal piglets. The nucleocapsid protein (N protein) of PEDV presents strong immunogenicity and contributes to the cross-reactivity between PEDV and TGEV. However, the characterization of epitopes on the PEDV N protein remains largely unknown. Here, two monoclonal antibodies (MAbs) specific to the N protein of a PEDV strain, FJzz1/2011, were generated and screened against a partially overlapping library of 24 GST-fusion N protein-truncated constructs. We confirmed that residues 18–133 (designated NEP-D4) and residues 252–262 (designated NEP-D6) were the epitopes targeted by MAbs PN-D4 and PN-D6, respectively. Sequence analysis revealed that these two epitopes were highly conserved among PEDV strains but were significantly different from other members of the Coronavirinae subfamily. Western blot analysis showed that they could be specifically recognized by PEDV antisera but could not be recognized by TGEV hyperimmune antisera. Indirect immunofluorescence (IFA) assays confirmed no cross-reaction between these two MAbs and TGEV. In addition, the freeze-thaw cycle and protease treatment results indicated that NEP-D4 was intrinsically disordered. All these results suggest that these two novel epitopes and their cognate MAbs could serve as the basis for the development of precise diagnostic assays for PEDV.


title: Efficiency and cell viability implications using tip type electroporation in zebrafish sperm cells

text: Sperm-mediated gene transfer (SMGT) has a potential use for zebrafish transgenesis. However, transfection into fish sperm cells still needs to be improved. The objective was to demonstrate the feasibility of tip type electroporation in zebrafish sperm, showing a protocol that provide high transfection efficiency, with minimal side-effects. Sperm was transfected with a Cy3-labelled DNA using tip type electroporation with voltages ranging from 500 to 1500 V. Sperm kinetics parameters were assessed using Computer Assisted Semen Analysis (CASA) and cell integrity, reactive oxygen species (ROS), mitochondrial functionality and transfection rate were evaluated by flow cytometry. The transfection rates were positively affected by tip type electroporation, reaching 64.9% ± 3.6 in the lowest voltage used (500 V) and 86.6% ± 1.9 in the highest (1500 V). The percentage of overall motile sperm in the electrotransfected samples was found to decrease with increasing field strength (P < 0.05). Increase in the sperm damaged plasma membrane was observed with increasing field strength (P < 0.05). ROS and sperm mitochondrial functionality did not present a negative response after the electroporation (P > 0.05). Overall results indicate that tip type electroporation enhances the internalization of exogenous DNA into zebrafish sperm cells with minimal harmful effects to sperm cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-020-05658-2) contains supplementary material, which is available to authorized users.


title: The potential for antibody-dependent enhancement of SARS-CoV-2 infection: Translational implications for vaccine development

text: There is an urgent need for vaccines to the 2019 coronavirus (COVID19; SARS-CoV-2). Vaccine development may not be straightforward, due to antibody-dependent enhancement (ADE). Antibodies against viral surface proteins can, in some cases, increase infection severity by ADE. This phenomenon occurs in SARS-CoV-1, MERS, HIV, Zika, and dengue virus infection and vaccination. Lack of high-affinity anti-SARS-CoV-2 IgG in children may explain the decreased severity of infection in these groups. Here, we discuss the evidence for ADE in the context of SARS-CoV-2 infection and how to address this potential translational barrier to vaccine development, convalescent plasma, and targeted monoclonal antibody therapies.


title: Sero‐prevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia

text: The Middle East Respiratory Syndrome Coronavirus (MERS‐CoV) is a novel Coronavirus which was responsible of the first case of human acute respiratory syndrome in the Kingdom of Saudi Arabia (KSA), 2012. Dromedary camels are considered as potential reservoirs for the virus and seem to be the only animal host which may transmit the infection to human. Further studies are required to better understand the animal sources of zoonotic transmission route and the risks of this infection. A primary sero‐prevalence study of MERS‐CoV preexisting neutralizing antibodies in Dromedary camel serum was conducted in Tabuk, western north region of KSA, in order to assess the seopositivity of these animals and to explain their possible role in the transmission of the infection to Human. One hundred seventy one (171) serum samples were collected from healthy dromedary camels with different ages and genders in Tabuk city and tested for specific serum IgG by ELISA using the receptor‐binding S1 subunits of spike proteins of MERS‐CoV. 144 (84,21%) of the total camel sera shown the presence of protein‐specific antibodies against MERS‐CoV. These results may provide evidence that MERS‐CoV has previously infected dromedary camels in Tabuk and may support the possible role of camels in the human infection.


title: The role of C/EBPβ phosphorylation in modulating membrane phospholipids repairing in LPS-induced human lung/bronchial epithelial cells

text: Abstract Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common critical emergency with high mortality in clinical practice. The key mechanism of ALI/ARDS is that the excessive inflammatory response damages the integrity of alveolar and bronchial cell membrane and thus affects their basic function. Phospholipids are the main component of cell membranes. Phospholipase A2 (PLA2), which catalyzes the cleavage of membrane phospholipids, is the most important inflammatory mediator of ALI. However, clara cell secretory protein 1 (CCSP1), an endogenous PLA2 inhibitor can increase the self-defense of membrane phospholipids. Thus, CCSP1 up-regulation and PLA2 inhibition constitutes an effective method for ensuring the stability of membrane phospholipids and for the treatment of ALI/ARDS. In the present study, we developed an in vitro model of ALI via lipopolysaccharide (LPS) stimulation of a human bronchial epithelial cell line, BEAS-2B, and assessed the mRNA and protein levels of CCSP1 and PLA2 in the model cells. The results demonstrated LPS induction inhibited the transcription and protein expression of CCSP1, but only the protein level of membrane associated PLA2 was increased, suggesting that in the in vitro ALI model, abnormally regulated CCSP1 transcription plays a crucial role in the damage of cell membrane. To find out the reason that CCSP1 expression was decreased in the ALI model, we predicted, by means of bioinformatics, putative transcription factors which would bind to CCSP1 promoter, examined their background and expression, and found that a transcription factor, CCAAT/enhancer binding protein β (C/EBP β), was correlated with the transcription of CCSP1 in the in vitro ALI model, and its phosphorylation in the model was decreased. CHIP-PCR and luciferase reporter assay revealed that C/EBP β bound to CCSP1 promoter and facilitated its transcription. Therefore, we conclude that there is a C/EBP β/CCSP1/PLA2 pathway in the in vitro ALI model. The study of underlying mechanism show that the activity of C/EBP β depends on its phosphorylation:LPS stimulation reduced C/EBP β phosphorylation and suppressed the transcription of CCSP1 in BEAS-2B cells, which resulted in enhanced PLA2 and the consequent membrane damage. And further study shows that overexpression of CDK2(Cyclindependent kinase 2), promoted the phosphorylation of C/EBP β and inhibited PLA2 through the C/EBP β/CCSP1/PLA2 pathway, so as to attenuate membrane damage. The significance of this study lies in that artificial C/EBP β phosphorylation regulation may ease the membrane damage in ALI and improve membrane repair.


title: Knowledge and attitudes towards Zika virus among medical students in King Abdulaziz University, Jeddah, Saudi Arabia

text: Abstract Zika Virus (ZIKV) and its associated consequences remain vital public health challenge of international concerns. The current study was done to assess knowledge and attitudes towards ZIKV and the factors associated with good knowledge among medical students in King Abdulaziz University, Jeddah. A cross-sectional study was conducted among 426 students. They were selected through multistage stratified random sample method, 2016. A validated, confidential, interviewing questionnaire contained 25 knowledge and 10 attitude items was used. Descriptive and inferential statistics were done. Results revealed that Facebook was the commonest source of ZIKV information. About half of the participants correctly identified mosquito bites and vertical route as ZIKV transmission modes. However, smaller percentages recognized the sexual and blood transmission modes. Calculations of knowledge score revealed that 77.5%, 15.0%, and 7.5% of the participants obtained poor, fair, and satisfactory scores, respectively. Age, educational year and attending ZIKV training were significantly associated with good knowledge (p< 0.05). Concerning attitudes, about half of the participants agreed that ZIKV could add new burden on healthcare system of the affected countries. Most of participants were interested in learning more about ZIKV, emerging diseases and travel epidemiology. In conclusion, medical students had limited knowledge about ZIKV, and good attitudes towards learning about it. Conduction of ZIKV educational programs, and development of courses about emerging disease epidemiology are required.


title: Alternative Multidisciplinary Management Options for Locally Advanced Non-Small Cell Lung Cancer During the COVID-19 Global Pandemic

text: Abstract: Importance The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation We present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus opinion of alternative strategies for the treatment of LA-NSCLC during a pandemic, though guiding data is scarce. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, attenuate the immunocompromising effects of lung cancer therapies, and provide effective oncologic therapy. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.


title: Compliance, safety concerns and anxiety in patients treated with biologics for psoriasis during the COVID‐19 pandemic national lockdown: a multicenter study in the Czech Republic

text: Patient concerns about the possible increased susceptibility to coronavirus disease 19 (COVID-19) infection or a more severe course of the disease when treated with immunosuppressive therapy may lead to lower treatment compliance.


title: Black Lives in a Pandemic: Implications of Systemic Injustice for End‐of‐Life Care

text: In recent months, Covid‐19 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long‐standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and end‐of‐life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. In the experience of many African American patients struggling against terminal illness, health care providers have denied them a say in their own medical decision‐making. In the midst of the Covid‐19 pandemic, African Americans have once again been denied a say with regard to the rationing of scarce medical resources such as ventilators, in that dominant and ostensibly race‐neutral algorithms sacrifice black lives. Is there such thing as a “good” or “dignified” death when African Americans are dying not merely of Covid‐19 but of structural racism?


title: Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

text: For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.


title: An Observational, Laboratory-Based Study of Outbreaks of Middle East Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014

text: Background. In spring 2014, a sudden rise in the number of notified Middle East respiratory syndrome coronavirus (MERS-CoV) infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, and changes in viral transmissibility, as well as diagnostic laboratory artifacts. Methods. Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of 4 single-nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture. Results. Up to 481 samples were received per day for reverse transcription polymerase chain reaction (RT-PCR) testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, whereas viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana (United States) and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, or serum neutralization. Conclusions. Virus shedding and virus functions did not change significantly during the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.


title: Characterization of a novel live attenuated infectious bronchitis virus vaccine candidate derived from a Korean nephropathogenic strain

text: A nephropathogenic K2/01 strain of infectious bronchitis virus (IBV) was attenuated by 170 serial passages in embryonated chicken eggs for possible use as a future IBV vaccine strain. High-growth properties and narrow tissue tropisms (limited replication in respiratory tracts) were achieved by the adaptation process. Unlike the parent strain, the attenuated strain (K2p170) was safe in day-old specific-pathogen-free chicks since replication of the virus did not induce mortality and nephritis, and rarely induced histological changes in the trachea and kidney after intraocular administration. In day-old broilers, even though coarse spray administration of K2p170 induced clinical signs, ciliostasis, and histopathological lesions in the trachea and the kidney, they were all comparable to birds vaccinated with commercial H120 vaccine. Despite restriction of viral replication in the respiratory tract, K2p170 elicited the production of antiserum with a neutralization index of 4.5. K2p170 provided almost complete protection against both two distinct subgroups of Korean nephropathogenic strain (KM91-like and QX-like subgroup). Furthermore, K2p170 provided significantly greater cross-protection against two heterologous strains (Massachusetts and Korean respiratory strain) than those conferred by the commercial H120 vaccine. K2p170 also had no virulence reversion after five back passages in chickens. In conclusion, K2p170 exhibits a fine balance between attenuation and immunogenicity, possesses cross-protective efficacy, and merits further investigation as a potential live vaccine as an alternative means of protection against the recently emergent nephropathogenic IBV infection in many Eurasian countries.


title: Unclear issues regarding COVID-19

text: Scientists from all over the world have been intensively working to discover different aspects of Coronavi-rus disease 2019 (COVID-19) since the first cluster of cases was reported in China. Herein, we aimed to investigate unclear issues related to transmission and pathogenesis of disease as well as accuracy of diagnostic tests and treatment modalities. A literature search on PubMed, Ovid, and EMBASE databases was con-ducted, and articles pertinent to identified search terms were extracted. A snow-ball search strategy was followed in order to retrieve additional relevant articles. It was reported that viral spread may occur during the asymptomatic phase of infection, and viral load was suggested to be a useful marker to assess disease severity. In contrast to immune response against viral infections, cytotoxic T lymphocytes decline in SARS-CoV-2 infection, which can be partially explained by direct invasion of T lymphocytes or apoptosis activated by SARS-CoV-2. Dysregulation of the urokinase pathway, cleavage of the SARS-CoV-2 Spike protein by FXa and FIIa, and consumption coagulopathy were the proposed mechanisms of the coagulation dysfunction in COVID-19. False-negative rates of reverse transcriptase polymerase chain reaction varied between 3% and 41% across studies. The probability of the positive test was proposed to decrease with the number of days past from symptom onset. Safety issues related to infection spread limit the use of high flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP) in hypoxic patients. Further studies are required to elucidate the challenging issues, thus enhancing the management of COVID-19 patients.


title: Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study

text: BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.


Various forms of skin rash in COVID-19 : a reply


title: Unidentified virus-like particles are detected in plasmas with elevated ALT levels: are they significant of etiological agent(s) of non-B, non-C hepatitis?

text: GB virus C (GBV-C) and hepatitis G virus (HGV) have been proposed as new viruses etiologically implicated in non-B, non-C hepatitis, but the morphology of these particular virus particles is still unknown, and most cases of non-A to E hepatitis do not relate to their infections. We tried to visualize virus-like particles (VLPs) in plasma samples from hepatitis B surface antigen- and antibody to hepatitis C virus (HCV)-negative blood donors with elevated alanine aminotransferase (ALT), and examined the association of the virus-like particles and the genomes of parenterally transmissible GBV-C/HGV. Twenty-three plasma samples, 13 with elevated ALT levels and 10 with normal ALT values, from blood donors without infections of hepatitis B virus (HBV) and HCV, were subjected to a 20%–60% sucrose density gradient centrifugation, and virus-like particles were observed by electron microscopy. GBV-C/HGV RNAs in the plasmas were tested. Virus-like particles were found in the fractions with densities of 1.15–1.16 g/ml from 12 of 13 (92.3%) plasmas with elevated ALT levels and 1 of 10 (10%) normal controls. The ultrastructural morphology of visualized VLPs was pleomorphic in size and appearance; the majority of the VLPs were 50- to 80-nm spherical particles with a 35- to 45-nm inner core and 9- to 12-nm-long surface spikelike projections. Rodlike VLPs 50–70 nm in diameter with a length of 110–160 nm were also observed in the same samples. The incidence of detection of the circulating VLPs was significantly (P < 0.001) related to elevated ALT levels, but GBV-C/HGV RNAs were detected in none of the plasmas containing the virus-like particles. Spherical VLPs are detected in HBV- and HCV-negative plasmas significantly correlated with the elevation of ALT, suggesting that they are implicated in non-B, non-C hepatitis.


title: Human respiratory syncytial virus and other viral infections in infants receiving palivizumab

text: Abstract Background Palivizumab is a humanized monoclonal antibody that prevents severe human respiratory syncytial virus (HRSV) infections. Objectives We determined the etiology of respiratory viral infections in palivizumab recipients, and monitored the clinical outcome and HRSV genotype in HRSV-infected infants. Study design Nasopharyngeal aspirates (NPAs) were collected from children receiving palivizumab who consulted or were hospitalized for acute respiratory tract infection (ARTI) during the 2004–2005 season. Viral cultures and multiplex RT-PCR for influenza A/B, HRSV and human metapneumovirus were performed. The fusion (F) gene of HRSV amplicons was also sequenced. Results Among 116 enrolled patients, 51 (44%) had ≥1 episode of ARTI for a total of 93 visits. At least one virus was identified in 33 (36%) of the 93 NPA samples; HRSV accounted for 11 (33%) of confirmed viral etiologies. Compared to subjects who had other viral ARTI, HRSV-positive subjects had less fever (p =0.01) and tended to have more bronchiolitis (p =0.07). Ten subjects (11 visits) developed HRSV infection, although only one was hospitalized. HRSV was detected after a median of 5.5 palivizumab doses and a median of 14 days after the last dose. One of the 11 HRSV strains tested had a F mutation located in the palivizumab-binding site. Conclusion HRSV is still a major cause of ARTI in children receiving palivizumab, although the outcome of infected children appears mild.


title: Efficacy of internet-based integrated intervention on depression and anxiety symptoms in patients with COVID-19

text: 目的: 目的探讨基于网络的整合心理干预对新冠肺炎患者抑 郁焦虑症状的有效性。 创新点: 创新点针对大规模公共卫生事件的患者, 首次采用基于 网络的整合心理干预技术开展抑郁焦虑症状的 治疗。这不仅能够让隔离患者更便捷地获得心理 干预, 而且减少了心理医生的感染暴露机会。 方法: 方法纳入26 例伴有抑郁焦虑症状的新冠肺炎患者, 随机分为干预组和对照组。干预组给予基于网络 的整合心理干预, 患者在医生指导下, 通过智能 手机聆听音频材料, 并接受整合心理干预, 包括 放松训练、正念治疗、“安全地”技术和蝴蝶拥 抱法; 对照组则给予支持性心理治疗。通过 HAMD-17 与HAMA 量表评估患者的抑郁焦虑水 平。我们发现在1 周末及2 周末干预组患者 HAMD-17 与HAMA 减分均明显优于对照组。 结论: 结论基于网络的整合心理干预可有效改善伴有抑郁焦 虑症状的新冠肺炎患者的情绪症状, 且对隔离患者 来说更便捷, 也减少了心理医生的感染暴露机会。


title: Neutrophil elastase inhibitory effects of pentacyclic triterpenoids from Eriobotrya japonica (loquat leaves)

text: Abstract Ethnopharmacological relevance Eriobotrya japonica, a traditional herbal medicine in China and Japan, has long been used to treat chronic bronchitis and coughs. Aim of the study Pentacyclic triterpenoids (PTs), especially ursolic acid (UA), have been found as reversibly and competitively human neutrophil elastase (HNE) inhibitors. However, the limited solubility and poor bioavailability of PTs hinder their clinical use. Crude plant extracts may have a greater activity than isolated constituents of the equivalent dosage. In this study, an Eriobotrya japonica (loquat leaves) extract (triterpenoid composition of loquat leaves, TCLL) with enriched PTs such as UA was prepared. The study aims to compare the HNE inhibitory (HNEI) effect in vitro and the therapeutic effect on acute lung injury (ALI) in vivo between TCLL and UA. Materials and methods An HNEI activity bioassay was performed with Sivelestat sodium hydrate as a positive control. A lipopolysaccharide (LPS)-induced lung inflammatory model was established to evaluate TCLL's therapeutic effect on ALI in vivo. The absorption of UA in TCLL and in UA alone was determined using a Caco-2 cell uptake model and LC-MS. Results The IC50 values of TCLL and UA for the HNEI effect were 3.26 ± 0.56 μg/mL and 8.49 ± 0.42 μg/mL (P < 0.01), respectively. TCLL significantly improved the inflammatory cells and inflammatory cytokine production in mice compared with the LPS group (P < 0.05). Additionally, it performed better than the UA alone group (P < 0.05). Moreover, the uptake by Caco-2 cells of UA in TCLL was higher than that in UA alone (P < 0.05). Conclusion TCLL has a significant HNEI effect in vitro and a therapeutic effect on LPS-induced inflammation in a mouse model. Both the effects are more efficient than UA. Improved absorption of PTs in TCLL may be one explanation for these results.


Coronavirus disease 2019 (COVID-19): we don’t leave women alone


title: The Relationship between Emotional Intelligence and Entrepreneurial Self-Efficacy of Chinese Vocational College Students

text: The purpose of this study is to explore the relationship between emotional intelligence and entrepreneurial self-efficacy. The sample consisted of 529 students. The tools used to measure the relationship between emotional intelligence and entrepreneurial self-efficacy were the Emotional Intelligence Scale developed by Wong and Law and the Entrepreneurial Self-Efficacy Scale developed by Zhan. The results showed that there was a significant difference between male and female college students in entrepreneurial self-efficacy, but no significant difference between male and female college students in emotional intelligence. In entrepreneurial self-efficacy as well as emotional intelligence, there were significant differences between the third grade and the first and second grade, respectively. In addition, the results showed a significant positive correlation between entrepreneurial self-efficacy and emotional intelligence. With the improvement of the emotional intelligence level of vocational college students, the entrepreneurial self-efficacy will increase. The lower the emotional intelligence, the faster the improvement in entrepreneurial self-efficacy. The higher the emotional intelligence, the more stable the entrepreneurial self-efficacy. The university stage is considered an ideal entrepreneurial period, especially for vocational colleges’ students, who pay more attention to entrepreneurship and innovation education. Encouraging the cultivation of the emotional intelligence of vocational college students in life will help to improve personal entrepreneurial self-efficacy. This research emphasizes that improving the emotional intelligence of vocational college students can enhance their sense of self-efficacy in entrepreneurship and help students with entrepreneurship and career development.


title: A Case of Coronavirus Infection Incidentally Found on FDG PET/CT Scan

text: We present a highly suspicious case of COVID-19 infection, incidentally found on (18)F-FDG PET/CT images. Patient was scanned on February, 25, 2020, when COVID-19 outbreak was unrecognized in our country. She admitted having recent occasional dry cough and fever. A retrospective review of her clinical and laboratory data was strongly suggestive for diagnosis of COVID-19 infection. PET/CT images demonstrated hypermetabolic diffuse ground glass opacities in both lungs with bilateral nodules. There was no evidence of pleural effusion or prominent mediastinal or hilar lymphadenopathy. Radiologists must be aware of COVID-19 presentations on PET/CT scan images during COVID-19 outbreak.


title: TRPV4: A Physio and Pathophysiologically Significant Ion Channel

text: Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.


title: Current status of personnel and infrastructure resources for infection prevention and control programs in the Republic of Korea: A national survey

text: BACKGROUND: There is significant variability in personnel and infrastructural resources for infection prevention and control (IPC) among health care institutions. The aim of this study is to evaluate the current status of individual hospital-based IPC programs in the Republic of Korea (ROK). METHODS: A multicenter cross-sectional survey of 100 hospitals participating in the national surveillance programs for multidrug-resistant organisms (MDROs) in the ROK was conducted in September 2015. The survey consisted of 140 standardized Web-based questionnaires. RESULTS: The survey response rate was 41.0%. The responding hospitals are largely organized with multibed rooms, with an insufficient numbers of single rooms. Employment status of infection specialists and hand hygiene resources were better in larger hospitals. The responding hospitals had 1 full-time infection control nurse per 400.3 ± 154.1 beds, with wide variations in training and experience. Facilities have great diversity in their approach to preventing MDROs. There appeared to be no difference in supplies consumption and protocols for IPC among the hospitals, stratified according to size. CONCLUSIONS: A greater availability of specialist personnel, single rooms, and a comprehensive IPC program, with the support of a policy-oriented management, is necessary to achieve effective IPC.


title: Something Else to Stress about: Perinatal Stress Attenuates CD8+ T Cell Activity in Adults

text: Summary Early-life stress has adverse health effects, but the underlying mechanisms are unclear. Hong et al. demonstrate that perinatal exposure to glucocorticoids in mice reprograms the neuroendocrine stress pathway. This results in reduced glucocorticoid levels in adults, leading to attenuated anti-tumor and anti-bacterial CD8+ T cell responses.


title: Post-natal follow-up for women and neonates during the COVID-19 pandemic: French National Authority for Health recommendations

text: INTRODUCTION: In the context of the stage 3 SARS-Cov-2 epidemic situation, it is necessary to put forward a method of rapid response for an HAS position statement in order to answer to the requests from the French Ministry of Solidarity and Health, healthcare professionals and/or health system users’ associations, concerning post-natal follow-up for women and neonates during the COVID-19 pandemic. METHODS: A simplified 7-step process that favours HAS collaboration with experts (healthcare professionals, health system users’ associations, scientific societies etc.), the restrictive selection of available evidence and the use of digital means of communication. A short and specific dissemination format, which can be quickly updated in view of the changes in available data has been chosen.


title: Safeguarding our future by protecting biodiversity

text: The Anthropocene is marked by twin crises: climate change and biodiversity loss. Climate change has tended to dominate the headlines, reflecting, in part, the greater complexity of the biodiversity crisis. Biodiversity itself is a difficult concept. Land plants dominate the global biomass and terrestrial arthropods probably dominate in terms of numbers of species, but most of the Tree of Life consists of single-celled eukaryotes, bacteria, and archaea. Wild plants provide a huge variety of products and services to people, ranging from those that are species-specific, such as food, medicine, and genetic resources, to many which are partly interchangeable, such as timber and forage for domestic animals, and others which depend on the whole community, but not on individual species, such as regulation of water supply and carbon sequestration. The use of information from remote sensing has encouraged a simplified view of the values of nature’s contributions to people, but this does not match the way most people value nature. We can currently estimate the proportion of species threatened by human impacts only for a few well-assessed groups, for which it ranges from 14% (birds) to 63% (cycads). Less than 8% of land plants have been assessed, but it has been estimated that 30-44% are threatened, although there are still few (0.2%) well-documented extinctions. Priorities for improving protection of biodiversity include: improving the inventory, with surveys focused on geographical areas and taxonomic groups which are under-collected; expanding the protected area system and its representativeness; controlling overexploitation; managing invasive species; conserving threatened species ex situ; restoring degraded ecosystems; and controlling climate change. The Convention on Biological Diversity (CBD) COP15 and the United Nations Framework Convention on Climate Change (UNFCCC) COP26 meetings, both postponed to 2021, will provide an opportunity to address both crises, but success will require high ambition from all participants.


title: Natural and experimental infection of neonatal calves with Clostridium difficile

text: Abstract Clostridium difficile toxins were associated with calf diarrhea in a recent retrospective study; however, no causal relationship has been prospectively investigated. This infection study tested whether the oral inoculation of neonatal calves with a toxigenic strain of C. difficile (PCR-ribotype 077) results in enteric disease. Fourteen 6–24h old male colostrums-fed Holstein calves, received either three doses of C. difficile (1.4×108 ±3.5×108 cfu) (n =8) or sterile culture broth (n =6). Calves were euthanized on day 6 or after the onset of diarrhea, whichever came first. Fecal and intestinal samples were blindly cultured for C. difficile, and tested for its toxin A/B (C. difficile TOX A/B II ELISA, Techlab). PCR-ribotyping was used to compare inoculated and recovered isolates. Diarrhea was observed in all control calves and 3/8 of inoculated calves (p =0.03), but it did not occur in calves that tested positive for C. difficile toxins. Fecal toxins were identified only from two controls. PCR-ribotyping confirmed the presence of C. difficile PCR-ribotype 077 in samples of all inoculated calves, but not from controls. The identification of five other PCR-ribotypes in 3/8 (37.5%) and 2/6 (33.3%) of inoculated and control calves, respectively, indicated early natural infection (≤24h of age). Five of 14 cecal samples had C. difficile (p =0.01). In conclusion, the oral administration of C. difficile PCR-ribotype 077 to neonatal calves resulted in fecal/intestinal colonization but not in detection of toxins, or signs of enteric disease. Further studies are required to investigate the clinical relevance of C. difficile in calves.


title: Syncytia Formation Induced by Coronavirus Infection Is Associated with Fragmentation and Rearrangement of the Golgi Apparatus

text: Abstract Coronavirus mouse hepatitis virus (MHV) possesses a membrane glycoprotein (M) which is targeted to the Golgi apparatus (GA). We used immunocytochemistry with an organelle-specific antiserum to investigate the morphologic changes of the GA during infection of L2 murine fibroblasts with MHV-A59. Twenty-four hours after infection the GA was fragmented and translocated in the center of syncytia, while the microtubular network was also rearranged displaying radiating elements toward the center of syncytia. Two fusion-defective mutants, which contain an identical amino acid substitution in the cleavage signal sequence of the spike glycoprotein (S), induced fragmentation of the GA. However, the GA migrated only partially to the centers of syncytia during infection with these mutants. Revertant viruses, in which the above mutation was corrected, had fusion properties and GA staining similar to wtMHV-A59. Experiments with brefeldin A (BFA), which induces redistribution of the GA into the rough endoplasmic reticulum (RER), revealed that an intact GA for a period of 4–16 hr postinfection, is required for coronavirus replication and syncytia formation. Thus, during MHV infection, syncytia formation is associated with fragmentation of the GA, followed by a previously undescribed phenomenon of migration of the organelle into the centers of syncytia. The fragmentation of the GA, however, may occur without the formation of syncytia. Therefore, two distinct mechanisms may be responsible for the fragmentation of the GA and its subsequent migration to the center of syncytia.


title: Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate

text: Abstract We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported.


title: Frequency of Continuous Renal Replacement Therapy Use Early in Coronavirus Disease 2019 Pandemic

text: OBJECTIVES: A subset of patients with coronavirus disease 2019 develop renal failure and require continuous renal replacement therapy. We reviewed the available literature to understand the frequency of continuous renal replacement therapy use among patients with coronavirus disease 2019 who required intensive care. DATA SOURCES: The authors reviewed PubMed and Google Scholar for published studies and MedRxiv.com for unpublished studies. STUDY SELECTION: Observational and randomized studies that report the frequency of continuous renal replacement therapy use in adult patients with coronavirus disease 2019. DATA EXTRACTION: Data from the eligible studies were extracted independently by two authors into Microsoft Excel. DATA SYNTHESIS: We identified 12 eligible studies (eight published, four unpublished). We found that up to 20% of patients admitted to ICUs may require continuous renal replacement therapy. CONCLUSIONS: Given the high utilization of continuous renal replacement therapy by critically ill patients with coronavirus disease 2019, there may be an urgent need to mobilize inpatient dialysis resources to cope with the anticipated increase in the demand.


title: A first step toward understanding patient safety

text: Patient safety has become an important policy agenda in healthcare systems since publication of the 1999 report entitled "To Err Is Human." The paradigm has changed from blaming the individual for the error to identifying the weakness in the system that led to the adverse events. Anesthesia is one of the first healthcare specialties to adopt techniques and lessons from the aviation industry. The widespread use of simulation programs and the application of human factors engineering to clinical practice are the influences of the aviation industry. Despite holding relatively advanced medical technology and comparable safety records, the Korean health industry has little understanding of the systems approach to patient safety. Because implementation of the existing system and program requires time, dedication, and financial support, the Korean healthcare industry is in urgent need of developing patient safety policies and putting them into practice to improve patient safety before it is too late.


title: Dynamic profiles, biodistribution and integration evaluation after intramuscular/intravenous delivery of a novel therapeutic DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in vaccinated normal rodent

text: BACKGROUND: The persistence, biodistribution, and risk of integration into the host genome of any new therapeutic DNA vaccine must be established in preclinical studies. We previously developed the DNA vaccine pcDNA-CCOL2A1 encoding chicken type II collagen (CCII) for the treatment of rheumatoid arthritis (RA). In the present study, we characterized its dynamic profile, biodistribution, and potential for genomic DNA integration in normal vaccinated rodent. RESULTS: A real-time quantitative PCR analysis (RT-qPCR) of animals administered a single dose of pcDNA-CCOL2A1 (300 μg/kg by intramuscular injection) showed that CCOL2A1 mRNA level in the blood peaked between 2 and 6 h post-immunization and then rapidly declined, and was undetectable between day 1–42. CCOL2A1 transcript was detected at the muscle injection site on days 3–14 post-immunization. Starting from day 14, the transcript was detected in the heart, liver, lung, and kidney but not in the spleen or thymus, and was expressed only in the lung on day 28. There was no CCOL2A1 mRNA present in the testes or ovaries at any time point. Non-invasive in vivo fluorescence imaging revealed CCII protein expression from 2 h up to day 10 and from 2 h up to day 35 after administration of pcDNA-CCOL2A1 via the intravenous and intramuscular routes, respectively; the protein had disappeared by day 42. Importantly, CCOL2A1 was not integrated into the host genome. CONCLUSIONS: These results indicate that pcDNA-CCOL2A1 vaccine is rapidly cleared within a short period of time and is therefore safe, and merits further development as a therapeutic vaccine for RA treatment.


title: Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

text: An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.


docid: ybjaksct

title: Prevalence of Venous Thromboembolism in Critically Ill Patients with COVID‐19

text: COVID‐19, the disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), was first reported in January 2020 (1, 2). It has become apparent that coagulopathy is a hallmark of the disease (3, 4). Additionally, thrombotic complications, including venous thromboembolism (VTE), have been reported to occur in 27‐69% of critically ill patients with SARS‐CoV‐2 (5‐9). As a result of these reports and other anecdotal evidence, many critically ill patients are receiving empiric therapeutic anticoagulation. Yet, experts generally recommend against the use of therapeutic anticoagulation prior to the development of VTE or another clinical indication (4, 10, 11).


title: Investigation of health care waste management in Binzhou District, China

text: Abstract In China, national regulations and standards for health care waste management were implemented in 2003. To investigate the current status of health care waste management at different levels of health care facilities (HCF) after the implementation of these regulations, one tertiary hospital, one secondary hospital, and four primary health care centers from Binzhou District were visited and 145 medical staff members and 24 cleaning personnel were interviewed. Generated medical waste totaled 1.22, 0.77, and 1.17kg/bed/day in tertiary, secondary, and primary HCF, respectively. The amount of medical waste generated in primary health care centers was much higher than that in secondary hospitals, which may be attributed to general waste being mixed with medical waste. This study found that the level of the HCF, responsibility for medical waste management in departments and wards, educational background and training experience can be factors that determine medical staff members’ knowledge of health care waste management policy. Regular training programs and sufficient provision of protective measures are urgently needed to improve occupational safety for cleaning personnel. Financing and administrative monitoring by local authorities is needed to improve handling practices and the implementation of off-site centralized disposal in primary health care centers.


title: Collaborative Multi-Disciplinary Incident Command at Seattle Children’s Hospital for Rapid Preparatory Pediatric Surgery Countermeasures to the COVID-19 Pandemic

text: Abstract Washington State was the first U.S. state to have a patient test positive for COVID-19. Prior to this, our children’s hospital proactively implemented an incident command structure which allowed for collaborative creation of safety measures, policies and procedures for both patients, families, staff and providers. Although the treatment and protective standards are continuously evolving, this commentary shares our thoughts on how an institution, specifically surgical services may develop collaborative process improvement to accommodate for rapid and ongoing change. Specific changes outlined include [1] early establishment of incident command [2] personal protective equipment conservation, [3] workforce safety, [4] surgical and ambulatory patient triage, and [5] optimization of trainee education. Please note that the contents of this manuscript are shared in the interest of providing collaborative information and are under continuous development as our regional situation changes. We recognize the limitations of this commentary and do not suggest that our approaches represent validated best practices.


title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection

text: Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.


title: Further Identification and Characterization of Novel Intermediate and Mature Cleavage Products Released from the ORF 1b Region of the Avian Coronavirus Infectious Bronchitis Virus 1a/1b Polyprotein

text: Abstract The coronavirus 3C-like proteinase is one of the viral proteinases responsible for processing of the 1a and 1a/1b polyproteins to multiple mature products. In cells infected with avian coronavirus infectious bronchitis virus (IBV), three proteins of 100, 39, and 35 kDa, respectively, were previously identified as mature cleavage products released from the 1b region of the 1a/1b polyprotein by the 3C-like proteinase. In this report, we show the identification of two more cleavage products of 68 and 58 kDa released from the same region of the polyprotein. In addition, two stable intermediate cleavage products with molecular masses of 160 and 132 kDa, respectively, were identified in IBV-infected cells. The 160-kDa protein was shown to be an intermediate cleavage product covering the 100- and 68-kDa proteins, and the 132-kDa protein to be an intermediate cleavage product covering the 58-, 39-, and 35-kDa proteins. Immunofluorescent staining of IBV-infected cells and cells expressing individual cleavage products showed that the 100-, 68-, and 58-kDa proteins were associated with the membranes of the endoplasmic reticulum, and the 39- and 35-kDa proteins displayed diffuse distribution patterns.


title: Cadre nosologique des infections respiratoires basses

text: Résumé Évoquer une infection respiratoire basse est aisé devant des signes respiratoires (toux, expectoration mucopurulente ou purulente) associés à des signes infectieux (fièvre notamment). En revanche, différencier bronchite et pneumonie est parfois plus difficile et constitue un enjeu important en raison de la mortalité des pneumonies et d'une prise en charge spécifique. L'élément clef du diagnostic est la radiographie de thorax dont l'indication repose sur des signes en foyer (crépitants, matité), une fièvre, une polypnée supérieure à 25/min, une tachycardie supérieure à 100/min. Leur valeur diagnostique n'est pas suffisante pour affirmer ou exclure une pneumonie ce qui justifie une radiographie en cas de doute clinique. Les éléments cliniques et radiologiques ne permettent pas un diagnostic étiologique fiable. L'analyse de l'expectoration, la recherche d'antigènes urinaires de pneumocoque et de Legionella constituent des éléments d'orientation. Le pneumocoque vient en tête des germes responsables de pneumonie, suivi par les germes atypiques et la légionellose. L'existence d'une bronchopneumopathie chronique obstructive (BPCO) expose au risque de décompensation et d'insuffisance respiratoire aiguë. Les causes d'exacerbation d'une BPCO sont multiples mais son origine infectieuse, notamment virale, est de l'ordre de 50 %. Les rhinovirus sont en cause dans 40 à 50 % des cas. D'autres virus peuvent être en cause et s'associer à la présence de bactéries (Streptococcus pneumoniae, Haemophilus influenzae, B. catarrhalis). L'appréciation de la gravité repose sur la connaissance du volume expiratoire maximal par seconde de base que l'Agence française de sécurité sanitaire des produits de santé propose de remplacer, lorsque ce paramètre n'est pas connu, par une appréciation de l'intensité de la dyspnée. Abstract Lower respiratory tract infection is easily suggested on clinical signs (cough and sputum) associated with fever. To discriminate between pneumonia and acute bronchitis is crucial because of the mortality associated with pneumonia and of its specific management. Chest X-ray is a key exam for the diagnosis and should be performed on the basis of validated clinical signs that are however of weak diagnostic value. Clinical as well as radiological signs cannot be reliably used to identify the causative germ. Sputum examination, the search for pneumococcal and legionella urinary antigens are of good diagnostic value. An associated COPD may lead to an acute respiratory failure. Acute exacerbation of chronic bronchitis results from various causes but infection is involved in about 50% of the cases, mostly viral and most often due to a rhinovirus. Viral infection can be associated to bacterial infection and the most frequently isolated germs are Streptococcus pneumoniae, Haemophilus influenzae, and B. catarrhalis. Severity assessment relies on the value of basal FEV1 that is often non available. Therefore Afssaps suggests using a dyspnea index to assess exacerbation severity.


title: Consensus of Chinese experts on protection of skin and mucous membrane barrier for health‐care workers fighting against coronavirus disease 2019

text: Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand‐cleaning‐ and medical‐glove‐related hand protection, mask‐ and goggles‐related face protection, UV‐related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.


title: Avoidable errors in the modelling of outbreaks of emerging pathogens, with special reference to Ebola

text: As an emergent infectious disease outbreak unfolds, public health response is reliant on information on key epidemiological quantities, such as transmission potential and serial interval. Increasingly, transmission models fit to incidence data are used to estimate these parameters and guide policy. Some widely used modelling practices lead to potentially large errors in parameter estimates and, consequently, errors in model-based forecasts. Even more worryingly, in such situations, confidence in parameter estimates and forecasts can itself be far overestimated, leading to the potential for large errors that mask their own presence. Fortunately, straightforward and computationally inexpensive alternatives exist that avoid these problems. Here, we first use a simulation study to demonstrate potential pitfalls of the standard practice of fitting deterministic models to cumulative incidence data. Next, we demonstrate an alternative based on stochastic models fit to raw data from an early phase of 2014 West Africa Ebola virus disease outbreak. We show not only that bias is thereby reduced, but that uncertainty in estimates and forecasts is better quantified and that, critically, lack of model fit is more readily diagnosed. We conclude with a short list of principles to guide the modelling response to future infectious disease outbreaks.